Moisturizing compositions and uses thereof

ABSTRACT

Embodiments herein are directed to moisturizing compositions comprising interpenetrating polymer networks, methods of making moisturizing compositions and methods of using moisturizing compositions.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Patent ApplicationNo. 62/294,706 filed on Feb. 12, 2016, and U.S. Provisional PatentApplication No. 62/394,540 filed on Sep. 14, 2016, the disclosures ofwhich are incorporated by reference in their entireties.

SUMMARY

Embodiments herein are directed to moisturizing compositions comprising:an interpenetrating polymer network made up of a crosslinked polypeptideor polysaccharide; a branched polymer with a hydrophobic modification;and a linear polypeptide or polysaccharide. In some embodiments, thecomposition is an interpenetrating polymer network comprising acrosslinked polypeptide or polysaccharide; a branched polymer with ahydrophobic modification; and a linear polypeptide or polysaccharide,wherein the crosslinked polypeptide or polysaccharide entraps theinterlaced branched polymer with a hydrophobic modification and thelinear polypeptide or polysaccharide to form the interpenetratingpolymer network.

Some embodiments are directed to methods of treating dry and/orirritated skin comprising administering a moisturizing compositioncomprising: an interpenetrating polymer network made up of a crosslinkedpolypeptide or polysaccharide; a branched polymer with a hydrophobicmodification; and a linear polypeptide or polysaccharide.

Some embodiments are directed to a method of producing aninterpenetrating polymer network moisturizing composition, the methodcomprising: dispersing a non-crosslinked polypeptide or polysaccharidecapable of crosslinking in water to form a first phase; combining alinear polypeptide or polysaccharide and a branched polymer with ahydrophobic modification with a humectant to form a second phase;combining the first and second phases to form a third phase ofuncrosslinked interlaced polymers, polypeptides, or polysaccharides;adding a mono-valent ion, di-valent ion or a combination thereof to thethird phase to crosslink one or more polypeptide, polymer, orpolysaccharide to form an interpenetrating polymer network moisturizingcomposition.

BRIEF DESCRIPTION OF THE FIGURES

The file of this patent contains at least one photograph or drawingexecuted in color. Copies of this patent with color drawings orphotographs will be provided by the Office upon request and payment ofnecessary fee.

FIG. 1 depicts the DVS weight versus time curve for formulation 1505-56.

FIG. 2 depicts the DVS weight change versus percent relative humiditycurve for formulation 1505-56.

FIG. 3 depicts the DVS weight versus time curve for formulation 1505-57.

FIG. 4 depicts the DVS weight change versus percent relative humiditycurve for formulation 1505-57.

FIG. 5 depicts the DVS weight versus time curve for formulation 1505-58.

FIG. 6 depicts the DVS weight change versus percent relative humiditycurve for formulation 1505-58.

FIG. 7 depicts the DVS weight versus time curve for formulation 1505-59.

FIG. 8 depicts the DVS weight change versus percent relative humiditycurve for formulation 1505-59.

FIG. 9 depicts improvements in clinical grading. FIG. 9A) Demonstratesimprovement in radiance after 1 week. FIG. 9B) Demonstrates improvementin fine lines after 1 week.

FIG. 10 depicts the improvement in moisture as measured by capacitanceusing the Corneometer over the course of the study.

FIG. 11 depicts 3 different subjects and the change in mean corneometermeasurements over the course of the study. FIG. 11A) Subject #7 withbaseline severe dry skin. FIG. 11B) Subject #16 with baseline moderatedry skin. FIG. 11C) Subject #14 with baseline mild dry skin.

FIG. 12 depicts improvement in conductance moisture measurements usingthe SKICON test.

FIG. 13 depicts the improvements in skin elasticity after 1 weekmeasured by the Cutometer.

FIG. 14 depicts the improvement in the skin as subjectively reported byeach individual. FIG. 14A) Improvement in radiance after 1 week. FIG.14B) Reported improvement in firmness. FIG. 14C) Improvement inplumpness after 1 week.

FIG. 15 provides a photograph of severe dry skin prior to theapplication of a moisturizing composition and a photograph of skin 15minutes after the application of formulation 1505-21.

FIG. 16A depicts the linear, branched, and crosslinked polymers,polypeptides, and polysaccharides in embodiments described herein. FIG.16B is a chemistry depiction of the 3D3P interpenetrating polymernetwork.

FIG. 17 shows the percent sample weight change by sorption under 5%relative humidity (RH) and 5%-95% RH.

FIG. 18 shows the mean corneometry scores for once daily use of 3D3P-IPNand commercial hydration product.

FIG. 19 shows VisioScan images for baseline and 8 weeks after treatmentwith formulation 1505-42B.

DETAILED DESCRIPTION

Traditional methods of hydrating skin (especially facial skin) are notsufficient especially in dry weather conditions. Commonly formulatedbarrier forming occlusive agents (petrolatum, high MW silicone fluids,plant butters) work well for reducing trans epidermal water loss butthese materials exhibit some undesired properties including theincreased potential of comedogenicity (clogging of pores). Occlusivematerials also do not attract/accumulate water at the skin's surfacewhich is limiting if one is trying to immediately improve the surfacehydration of human skin. Commonly formulated humectants (i.e. glycols,glycerin, hyaluronic acid, or PCA salts) attract water to the skin'ssurface but these materials also exhibit undesirable properties whichcan include a lingering tackiness or stickiness and product pilling orflaking off skin. As a result humectants are often formulated at uselevels far below 10% in moisturizing skin care products. There is a needto increase concentrations of humectant and osmolytic ingredients toachieve a more significant and immediate hydrating effect which canalter skin's appearance by plumping dry skin to visibly reduce theappearance of wrinkles. Improvements can be made with moisture bindingpolysaccharides such as, but not limited to hyaluronic acid to increasedeposition and/or adherence and interaction on the skin's surface.

Without wishing to be bound by theory, the compositions of the presentinvention cannot be formed by merely mixing the individual componentstogether; such a method would produce a composition with a differentstructure and having a much lower viscosity than is desirable. Forexample, the dynamic viscosity of the same polymers at the sameconcentrations in the same solvent system without an interpenetratingpolymer network is between 100-300 cps. Embodiments of presentcompositions are formed when the method steps described in theembodiments herein are followed. The order of the steps described hereinproduce an interpenetrating polymer network (IPN) with beneficialproperties as described herein. In embodiments, the linear polypeptideor polysaccharide and branched polymer with a hydrophobic modificationare mixed together first and must interlace, the non-crosslinkedpolypeptide or polysaccharide capable of being crosslinked is then addedto the mixture of the linear polypeptide or polysaccharide and branchedpolymer with a hydrophobic modification e before the crosslinking can beinitiated. Upon the addition of divalent salts and cooling, thecrosslinkable polypeptide or polysaccharide becomes cross-linked andentraps the other ingredients, thereby forming the IPN. In embodiments,the dynamic viscosity of the claimed IPN of the present invention ismuch greater than the viscosity of the individual components simplymixed together and is between about 400-1400 cps. This resulting IPN hasa thixotropic rheology with a substantive skin feel on application whichprovides the beneficial properties described in the embodiments herein.Embodiments herein are directed to moisturizing composition comprising:an interpenetrating polymer network made up of a crosslinked polypeptideor polysaccharide; a branched polymer with a hydrophobic modification;and a linear polypeptide or polysaccharide. In some embodiments thecomposition is an interpenetrating polymer network comprising acrosslinked polypeptide or polysaccharide; a branched polymer with ahydrophobic modification; and a linear polypeptide or polysaccharide,wherein the crosslinked polypeptide or polysaccharide entraps theinterlaced branched polymer with a hydrophobic modification and thelinear polypeptide or polysaccharide to form the interpenetratingpolymer network. In some embodiments, the interpenetrating polymernetwork is a de-tackified interpenetrating polymer network for topicalhumectant delivery. In some embodiments, the compositions describedherein can be used to treat and/or prevent dry skin by delivering agentsknown to promote normalization of epidermal proliferation anddifferentiation such as but not limited to calcium PCA,phosphatidylglycerol, and mixtures of ceramides. In some embodiments,the compositions described herein have superior sensorial properties andwater binding properties. In yet other embodiments, the compositionsdescribed herein lack the undesired sensorial tackiness associated withdry-down during application of typical hydrogels. As a result, thecompositions described herein deliver a superior sensorial experienceduring application.

Dry skin is a persistent problem and especially aggravated in lowrelative humidity conditions and during seasonal weather transitions.The biological implications with regard to keratinocyteunder-differentiation and over proliferation in dry skin have recentlycome to light and there is a need for more concentrated delivery ofhumectants in a cosmetically suitable preparation. The compositions haveunique physical properties (hydrophobic-like, adhesive, non-sticky,quick spreading, film forming with high affinity for the skin's surface)to aid the delivery of humectants capable of dissolving desmosomes toassist in desquamation and deliver other agents which promote thedifferentiation of keratinocytes to normalize over proliferationassociated with dry skin.

The use of humectants for improving surface moisture levels of humanskin is well established in the art of skin care formulation. Thispractice includes a wide range of both polymeric and non-polymericsubstances. Having a high affinity for water, humectant substancesabsorb and retain water from air. Typically humectant substances whichare commonly applied on skin for hydration benefits consist of compoundswith hydrophilic groups including hydroxyl, amine, carboxyl and salts.One challenge in applying these materials to human skin includes theundesired sensorial effects of stickiness or tackiness which accompanythe most popular topical humectants including hyaluronic acid andglycerin. While the FDA identifies glycerin formulated at 30% as an OTCskin protectant it is rare to find commercially available products whichutilize glycerin at 10% or above. Equally many humectant polysaccharidesincluding hyaluronic acid are only utilized at minimal levels in skincare formulations to also avoid the undesired sensorial properties ofglue-like stickiness and tackiness which is inherent in these gum-likesubstances. A need exists for treating dry skin with more significantconcentrations of humectants with minimized stickiness and tackiness toalleviate dry skin for prolonged periods without the need of constantproduct reapplications.

The present invention is directed to compositions including, and methodsof preparing, an interpenetrating polymer network capable of topicallydelivering extremely high levels of humectants with significantlyminimized undesired stickiness and a superior sensorial experience. Thepresent invention is also directed to the use of these compositions totreat and/or prevent dry and/or irritated skin. More specifically, theinventors have identified the correct balance/ratio of carboxyl groupsto hydroxyl groups which alter the aesthetic sensorial properties ofboth the polymer and non-polymer humectants such as, but not limited toglycerin and hyaluronic acid while in the context of a 3-dimensionalinterlaced polymer network. As a result, humectants, such as, but notlimited to, glycerin, can be applied to the skin at concentrations of30% or above without the undesired effects of stickiness to yieldsignificant and prolonged hydration of dry and irritated skin.

Although any methods and materials similar or equivalent to thosedescribed herein can be used in the practice or testing of embodimentsof the present invention, the exemplary methods, devices, and materialsare now described.

The term “comprising” means “including, but not limited to.” The term“consisting essentially of” means the method or composition includes thesteps or components specifically recited, and may also include thosethat do not materially affect the basic and novel characteristics of thepresent invention. The term “consisting of” means the method orcomposition includes only the steps or components specifically recited.

In each of the embodiments disclosed herein, the compounds and methodsmay be utilized with or on a subject in need of such treatment, whichmay also be referred to as “in need thereof.” As used herein, the phrase“in need thereof” means that the subject has been identified as having aneed for the particular method or treatment and that the treatment hasbeen given to the subject for that particular purpose.

As used herein, the term “Interpenetrating polymer network” (IPN) meansa polymer comprising two or more networks which are at least partiallyinterlaced on a polymer/molecular scale but not covalently bonded toeach other and cannot be separated unless chemical bond(s), for example,in at least one of the networks, are broken. In some embodiments, thetwo or more networks can be envisioned to be entangled in such a waythat they are concatenated and cannot be pulled apart, but not bonded toeach other by any chemical bond. In other words, an InterpenetratingPolymer Network (IPN) is to a scaffold or three dimensional structurethat is formed by the processes described herein. The IPN is composed ofone or more crosslinked polymer, polypeptide or polysaccharide and oneor more polymer, polypeptide, polysaccharide, or other agent which havebeen entrapped within the crosslinked polymer, polypeptide orpolysaccharide A mixture of two or more pre-formed polymer networks isnot an IPN.

As used herein, the term “crosslinked” refers to the ionic bond formedand change in tertiary structure of the polymer, polypeptide orpolysaccharide upon the addition of mono- or di-valent ions to andcooling of the third phase to form the IPN.

As used herein, the term or phrase “crosslinkable” or “non-crosslinkedcapable of crosslinking” refers to the polymer, polypeptide orpolysaccharide in its initial state before the crosslinking process hasoccurred.

As used herein, a “semi-interpenetrating polymer network” (SIPN): meansa polymer comprising one or more networks and one or more linear orbranched polymer(s) characterized by the penetration on a molecularscale of at least one of the networks by at least some of the linear orbranched macromolecules. Semi-interpenetrating polymer networks aredistinguished from interpenetrating polymer networks because theconstituent linear or branched polymers can, in principle, be separatedfrom the constituent polymer network(s) without breaking chemical bonds;they are polymer blends.

As used herein, a “sequential interpenetrating polymer network” means aninterpenetrating polymer network prepared by a process in which thesecond component network is formed following the formation of the firstcomponent network.

As used herein, a “sequential semi-interpenetrating polymer network”means a semi-interpenetrating polymer network prepared by a process inwhich the linear or branched components are formed following thecompletion of the reactions that lead to the formation of the network(s)or vice versa.

As used herein, the term “patient” and “subject” are interchangeable andmay be taken to mean any living organism, which may be treated withcompounds of the present invention. As such, the terms “patient” and“subject” may include, but is not limited to, any non-human mammal,primate or human. In some embodiments, the “patient” or “subject” is anadult, child, infant, or fetus. In some embodiments, the “patient” or“subject” is a human. In some embodiments, the “patient” or “subject” isa mammal, such as mice, rats, other rodents, rabbits, dogs, cats, swine,cattle, sheep, horses, primates, or humans.

As used herein, the terms “adjunctive administration” and “adjunctively”may be used interchangeably, and refer to simultaneous administration ofmore than one compound in the same dosage form, simultaneousadministration in separate dosage forms, and separate administration ofmore than one compound as part of a single therapeutic regimen.

As used herein the term ‘topical formulation’ refers to a formulationthat may be applied to skin or a mucosa. Topical formulations may, forexample, be used to confer therapeutic benefit to a patient or cosmeticbenefits to a consumer. Topical formulations can be used for bothtopical and transdermal administration of substances.

The term ‘topical administration’ is used in its conventional sense tomean delivery of a substance, such as a therapeutically active agent, tothe skin or a localized region of the body.

The term ‘transdermal administration’ is used to mean administrationthrough the skin. Transdermal administration is often applied wheresystemic delivery of an active is desired, although it may also beuseful for delivering an active to tissues underlying the skin withminimal systemic absorption.

Before the present compositions and methods are described, it is to beunderstood that this invention is not limited to the particularprocesses, compositions, or methodologies described, as these may vary.Moreover, the processes, compositions, and methodologies described inparticular embodiments are interchangeable. Therefore, for example, acomposition, dosages regimen, route of administration, and so ondescribed in a particular embodiments may be used in any of the methodsdescribed in other particular embodiments. It is also to be understoodthat the terminology used in the description is for the purpose ofdescribing the particular versions or embodiments only, and is notintended to the limit the scope of the present invention which will belimited only by the appended claims. Unless defined otherwise, alltechnical and scientific terms used herein have the same meanings ascommonly understood by one of the ordinary skill in the art. Althoughany methods similar or equivalent to those describe herein can be usedin the practice or testing of embodiments of the present invention, thepreferred methods are now described. All publications and referencesmentioned herein are incorporated by reference. Nothing herein is to beconstrued as an admission that the invention is not entitled to antedatesuch disclosure by virtue of prior invention.

It must be noted that, as used herein, and in the appended claims, thesingular forms “a”, “an” and “the” include plural reference unless thecontext clearly dictates otherwise.

As used herein, the term “about” means plus or minus 10% of thenumerical value of the number with which it is being used. Therefore,about 50% means in the range of 45%-55%.

“Optional” or “optionally” may be taken to mean that the subsequentlydescribed structure, event or circumstance may or may not occur, andthat the described includes instances where the event occurs andinstances where it does not.

“Administering” when used in conjunction with a therapeutic means toadminister a therapeutic directly or indirectly into or onto a targettissue to administer a therapeutic to a patient whereby the therapeuticpositively impacts the tissue to which it is targeted. “Administering”may include the act of self-administration or administration by anotherperson such as a health care provider.

The term “improves” is used to convey that the present invention changeseither the appearance, form, characteristics, structure, function and/orphysical attributes of the tissue to which it is being provided, appliedor administered. “Improves” may also refer to the overall physical stateof an individual to whom an active agent has been administered. Forexample, the overall physical state of an individual may “improve” ifone or more symptoms of the disease, condition or disorder arealleviated by administration of an active agent.

The term “cosmetic” means an agent utilized, and/or intended to beapplied to the human body for cleansing, beautifying, promotingattractiveness, altering the appearance of the skin or any combinationthereof.

The terms “effective amount” or “effective dose” as used herein areinterchangeable and may refer to the amount of an active agent orcompound or composition that has the effect of moisturizing, cleansing,beautifying, promoting attractiveness, altering the appearance of theskin, or any combination thereof, that is being sought by the user. Insome embodiments, “effective amount” or “effective dose” as used hereinare interchangeable and may refer to the amount of an active agent orcompound or composition that has the effect of promoting the exfoliationof dry skin, promoting the digestion of desmosomes, normalizing cellmaturation, modulating keratinocyte function, normalizing keratinocytedifferentiation, normalizing keratinocyte proliferation, modulatingphosphatidylglycerol content of keratinocytes, modulating and/orimproving the moisture content of the skin, promoting the retention oflong lasting hydration in the skin, increasing skin moisture, improvingskin water balance, increasing skin hydration, decreasing transepidermalwater loss, reducing evaporation of water from the skin, treating and/orpreventing dry and/or irritated skin, defending against, and reducingvisible signs of aging for noticeably firmer, smoother, and flawlesslooking skin, erasing the appearance of premature aging, including brownspots, dullness and discoloration, visibly brightening the skin,reducing the appearance of fine lines and wrinkles, creating a radiantcomplexion, shielding the skin again biological and environmentalaggressors associated with dry, irritated and sensitive skin, helpingthe skin retain moisture and remain comfortable when challenged byclimate and other environmental aggressors, rehydrating the skin, torepairing, renewing, and/or enhancing the skin's natural moisturebarrier.

The term “treating” may be taken to mean prophylaxis of a specificdisorder, disease or condition, alleviation of the symptoms associatedwith a specific disorder, disease or condition and/or prevention of thesymptoms associated with a specific disorder, disease or condition. Insome embodiments, the term refers to slowing the progression of thedisorder, disease or condition or alleviating the symptoms associatedwith the specific disorder, disease or condition. In some embodiments,the term refers to alleviating the symptoms associated with the specificdisorder, disease or condition. In some embodiments, the term refers toalleviating the symptoms associated with the specific disorder, diseaseor condition. In some embodiments, the term refers to restoring functionwhich was impaired or lost due to a specific disorder, disorder orcondition.

The term “inhibit,” “suppress,” “decrease,” “interfere,” and/or “reduce”(and like terms) generally refers to the act of reducing, eitherdirectly or indirectly, a function, activity, or behavior relative tothe natural, expected, or average or relative to current conditions.

The term “increase,” “enhance,” “stimulate,” and/or “induce” (and liketerms) generally refers to the act of improving or increasing, eitherdirectly or indirectly, a function or behavior relative to the natural,expected, or average or relative to current conditions.

The term “modulate,” “modify,” and/or “modulator” generally refers tothe act of directly or indirectly promoting/stimulating or interferingwith/inhibiting a specific function or behavior. In some instances amodulator may increase and/or decrease a certain activity or functionrelative to its natural state or relative to the average level ofactivity that would generally be expected or relative to a current levelof activity.

As used herein, the term “normalize” refers to the act of establishingand/or maintaining a relative balance or equilibrium between two or moreactivities, functions or conditions.

The term “cosmetic composition” shall mean a composition including atleast one active ingredient, whereby the composition is amenable toinvestigation for a specified, efficacious outcome in a mammal (forexample, without limitation, a human). Those of ordinary skill in theart will understand and appreciate the techniques appropriate fordetermining whether an active ingredient has a desired efficaciousoutcome based upon the needs of the artisan.

As used herein, the term “topically” and “topical” refers to applicationof the compositions of the present invention to the surface of the skinand mucosal cells and tissues.

Embodiments herein are directed to moisturizing compositions consistingessentially of: an interpenetrating polymer network made up of acrosslinked polypeptide or polysaccharide; a branched polymer with ahydrophobic modification; and a linear polypeptide or polysaccharide.Embodiments herein are directed to moisturizing compositions consistingof: an interpenetrating polymer network made up of a crosslinkedpolypeptide or polysaccharide; a branched polymer with a hydrophobicmodification; and a linear polypeptide or polysaccharide. Embodimentsherein are directed to moisturizing compositions comprising: aninterpenetrating polymer network made up of a crosslinked polypeptide orpolysaccharide; a branched polymer with a hydrophobic modification; anda linear polypeptide or polysaccharide. In some embodiments, thecomposition is an interpenetrating polymer network comprising acrosslinked polypeptide polysaccharide; a branched polymer with ahydrophobic modification; and a linear polypeptide or polysaccharide,wherein the crosslinked polypeptide or polysaccharide entraps theinterlaced branched polymer with a hydrophobic modification and thelinear polypeptide or polysaccharide to form the interpenetratingpolymer network. In some embodiments, the polypeptide or polysaccharidecapable of crosslinking, the branched polymer with a hydrophobicmodification and the linear polypeptide or polysaccharide form aninterpenetrating polymer network.

In some embodiments, the compositions described herein comprisinginterpenetrating polymer networks act as a moisture delivery scaffoldfor water, glycerin, other small molecule humectants and osmolytes whichcan be introduced at high concentrations of about 30-45% of the totalcomposition. In some embodiments, the ratio of the humectants to theinterpenetrating polymer networks in the compositions described hereinis very important and unique as it may alter the physical properties ina way which confers to the composition more hydrophobic characteristics.Without wishing to be bound by theory, the hydroxyl groups of glycerinand glycols hydrogen bond with the hydroxyl groups of thepolysaccharides to a point where the hydrogen-bonding groups satisfyeach other. Thus, in some embodiments, the compositions described hereinhave a sensorial skin feel which is more like a slippery silicone oilwhich exhibits no stickiness, tackiness or pilling. After product drydown on skin, water applied starts to bead as though the composition wasprepared from hydrophobic oils or waxes. In some embodiments, thecompositions described herein have other unique physical propertiesincluding, but not limited to, an increase gelling and viscosity withthe addition of cosmetic grade acids (e.g. lactic acid, citric acid,glycolic acid). It is common knowledge that most cosmetic gel structuresdecrease in viscosity with the addition of acids. The unique physicalproperties achieved from the compositions described herein allow fordelivering high levels of humectants which behave partially likeocclusive barrier agents. In some embodiments, the compositionsdescribed herein have a high deposition characteristic on glass, plasticand human skin. In some embodiments, the compositions described hereindemonstrate a significant improvement in surface hydration of human skineven 8 hours after application. In some embodiments, the compositionsdescribed herein are capable of delivering agents which promotekeratinocyte differentiation.

In some embodiments, the compositions described herein comprisinginterpenetrating polymer networks act as a drug or active ingredientdelivery scaffold for skin treatments, acne treatments, wrinkletreatments, or anti-inflammatory agents, In some embodiments, the acnetreatment is selected from the group consisting of benzoyl peroxide,salicylic acid, willowbark extract, poly hydroxyacid, tannic acid,hydroxybenzoic acid, juniperic acid, tartaric acid, glycolic acid,lactic acid, and citric acid. In some embodiments, the wrinkle treatmentis selected from the group consisting of retinol, antioxidants, vitaminA, retinoid, tretinoin, and tazarotene. In some embodiments, theanti-inflammatory agent is selected from the group consisting ofibuprofen, diclofenac, felbinac, ketoprofen, and piroxicam.

Embodiments herein are directed to a delivery system comprising aninterpenetrating polymer network made up of a crosslinked polypeptide orpolysaccharide; a branched polymer with a hydrophobic modification; alinear polypeptide or polysaccharide; and an active ingredient; whereinthe crosslinked polypeptide or polysaccharide entraps the interlacedbranched polymer with a hydrophobic modification and the linearpolypeptide or polysaccharide to form the interpenetrating polymernetwork.

In some embodiments, the crosslinked polypeptide or polysaccharide isselected from the group consisting of crosslinked gellan gum,crosslinked carrageenan, crosslinked chitosan, crosslinked xanthan gum,sodium polyglutamate crosspolymer, polydextrose, and combinationsthereof. In some embodiments, the crosslinked polypeptide orpolysaccharide is crosslinked gellan gum.

In some embodiments, interpenetrating polymer networks such as thosedescribed herein can be used to deposit and/or deliver agents such as,but not limited to, water, humectants, natural moisturizing factors,osmolytes, bio-active hydrators, and keratinocyte differentiationpromoting agents. In some embodiments, surface spreading and contactwith skin is improved when the interpenetrating polymer networkcomprises a hydrophobically modified polymer.

In some embodiments, the branched polymer with a hydrophobicmodification is selected from the group consisting of hydrophobicallymodified hydroxypropylmethylcellulose, hydrophobically modified cetylhydroxy propyl methyl cellulose, hydrophobically modified sodium acetylhyaluronate, hydrophobically modified cetyl hydroxyethylcellulose,hydrophobically modified starch, hydrophobically modifiedcarboxymethylchitosan, and combinations thereof. In some embodiments,the branched polymer with a hydrophobic modification is hydrophobicallymodified cetyl hydroxyethylcellulose.

In some embodiments, the linear polypeptide or polysaccharide isselected from the group consisting of gellan gum, carrageenan, xanthangum, biosaccharide gum-1, sclerotium gum, pectin, pullulan, guar gum,gum arabic, chondroitin, sulfate, alginic acid, sodium hyaluronate,hydrolyzed hyaluronic acid sodium polyglutamate, chitin, chitosan,starch, and combinations thereof. In some embodiments, the linearpolypeptide or polysaccharide is sodium hyaluronate.

In some embodiments, the crosslinked polypeptide or polysaccharide,branched polymer with a hydrophobic modification; and linear polypeptideor polysaccharide comprise from about 0.01% to about 5% of thecomposition by weight.

In some embodiments, the moisturizing composition further comprises amono-, or di-valent ion. In some embodiments, the mono-, or di-valention is selected from the group consisting of 2-Pyrrolidone-5-CarboxylicAcid and related salts, calcium PCA, sodium PCA, zinc PCA, magnesiumPCA, sea salt, inorganic salts of citric acid, inorganic salts of lacticacid, calcium ascorbate, magnesium ascorbate, calcium oxide, calciumbenzoate, calcium sorbate, calcium aspartate, magnesium carbonate,magnesium chloride, magnesium nitrate, and any combination thereof. Insome embodiments, the mono-, or di-valent ion includes calcium PCA,magnesium PCA, and sea salt. Without wishing to be bound by theory,mono- and di-valent salts such as, but not limited to calcium PCA andMagnesium PCA can facilitate the cross-linking of a linear polypeptideor polysaccharide such as, but not limited to, gellan gum into aninterpenetrating polymer network. In some embodiments, the mono-, ordi-valent ion comprises between about 0.01% to about 5% of thecomposition by weight.

In some embodiments, the moisturizing compositions further comprises atleast one humectant. In some embodiments, the at least one humectant isselected from the group consisting of glycerin, diglycerin, betaine,diols, propylene glycol, butylene glycol, pentylene glycol, propanediol,1,2-hexanediol, D-ribose, glucose, sorbitol, dextrose, urea,2-Pyrrolidone-5-Carboxylic Acid and related salts, sea salt, inorganicsalts of citric acid, inorganic salts of lactic acid, ectoin, lacticacid, betaine, glycolic acid, lactobionic acid, and any combinationthereof. In some embodiments, the humectant includes glycerin andpentylene glycol. In some embodiments, the humectant comprises at leastabout 30% of the composition by weight. In some embodiments, thehumectant comprises between about 25% to about 80% of the composition byweight.

In some embodiments, the moisturizing composition further comprises anactive agent. In some embodiments, the active agent is selected from thegroup consisting of glycerin, diglycerin, betaine, diols, propyleneglycol, butylene glycol, pentylene glycol, propanediol, 1,2-hexanediol,D-ribose, glucose, sorbitol, dextrose, urea, 2-Pyrrolidone-5-CarboxylicAcid and related salts, sea salt, inorganic salts of citric acid,inorganic salts of lactic acid, ectoin, lactic acid, betaine, glycolicacid, lactobionic acid, and any combination thereof. In someembodiments, the active agent is a cell cycle modulator. In someembodiments, the cell cycle modulator is selected from the groupconsisting of phosphatidylglycerol, calcium PCA, Lysolecithin, and anycombination thereof. Without wishing to be bound by theory, increasingmoisture content at the skin's surface may not be enough as a long termstrategy for combating the effects of dry skin. It is believed that thekeratinocyte cell cycle has implications on dry skin. In biopsy studies,epidermal under-differentiation appears to be linked with dry skin inboth young and old populations. In some embodiments, other cellularmodulations can also be considered such as gene expression manipulationof AQP3 for improving skin hydration via cellular glycerol/waterchannels.

In some embodiments, the moisturizing composition further comprises akeratinocyte differentiation promoting agent. In some embodiments, thekeratinocyte differentiation promoting agent is selected from the groupconsisting of phosphatidylglycerol, an organic salt ofglycerophosphoinositol, calcium PCA, calcium lactate, calcium citrate orother forms of soluble calcium, hydroxyapatite, cortisone, ceramides,ergocalciferol, cholecalciferol, sphingolipids, and any combinationthereof.

In some embodiments, the moisturizing compositions described herein mayfurther comprise a preservative system. In some embodiments, thepreservative system may comprise phenoxyethanol, capryl glycol,ethylhexylglycerin, hexylene glycol, sodium benzoate, potassium sorbate,methyl paraben, gluconolactone, lactic acid, sorbic acid, glycerylcaprylate, glyceryl undecylenate, ethanol, chlorphenesin, salicylic acidor any combination thereof. In some embodiments, the preservative systemmay comprise phenoxyethanol and capryl glycol and ethylhexylglycerin andhexylene glycol. In yet other embodiments, the preservative system maycomprise glyceryl caprylate and glyceryl undecylenate.

In some embodiments, the moisturizing compositions described herein mayfurther comprise caprylyl methicone-cosmetic silicone, PEG-12dimethicone/PPG-20 Crosspolymer, alcohol denatured, isododecane,polysilicone-11, Dimethylacrylamide/Acrylic Acid/Polystyrene EthylMethacrylate Copolymer, coco-caprylate/Caprate, decyl glucoside,Hydroxyethyl Acrylate/Sodium Acryloyldimethyl Taurate Copolymer,Isohexadecane, and polysorbate 60.

The moisturizing compositions of the present invention may be formulatedby those skilled in the art as liquids, solutions, emulsions, creams,lotions, suspensions, triturates, gels, jellies, foams, pastes,ointments, shampoos, adhesives and the like.

The moisturizing compositions of the present invention result in animproved capacity to absorb, attract, and bind water. The ability of acomposition to absorb and retain water can be measured by Karl Fischerwater content analysis and dynamic vapor sorption (DVS) analysis. Inembodiments described herein, moisturizing compositions have greaterthan 25% water content as measured by Karl Fischer water contentanalysis. In embodiments described herein, moisturizing compositionshave a weight gain between 10% and 100% from 5% to 95% relative humidityas measured by DVS.

The following paragraphs describe moisturizing compositions produced bythe process described herein and it is understood that particularingredients will fall under one of the categories comprising theinterpenetrating polymer network.

In some embodiments, the moisturizing composition comprises SodiumHyaluronate, Cetyl hydroxyethylcellulose, Gellan Gum, Glycerin,Pentylene Glycol, Magnesium PCA, Calcium PCA, and Sea Salt Fine.

In some embodiments, the moisturizing composition comprises DI Water,Glycerin, Phosphatidylglycerol, Pentylene Glycol, Bis-PEG-12Dimethicone, Sodium Hyaluronate, Pyrus Malus (Apple) Fruit Extract,Phenoxyethanol, Capryl Glycol, Ethylhexylglycerin, Hexylene glycol,Calcium PCA, Gellan Gum, Magnesium PCA, Cetyl hydroxyethylcellulose, SeaSalt Fine, and Sodium benzoate.

In some embodiments, the moisturizing composition comprises DI Water,Glycerin, Pentylene Glycol, Bis-PEG-12 Dimethicone, Sodium Hyaluronate,Cetyl hydroxyethylcellulose, Adenosine, Magnesium PCA, Calcium PCA,Sodium benzoate, Sea Salt Fine, Pyrus Malus (Apple) Fruit Extract,Lactic acid, Kelcogel CG-HA Gellan Gum, Kelcogel CG-LA Gellan Gum,Phosphatidylglycerol, Ceteareth-25, Cetyl Alcohol, Behenic Acid,Cholesterol, Ceramide NP, Ceramide NS, Ceramide EOS, Ceramide EOP,Ceramide AP, Caprooyl Phytosphingosine, Caprooyl Sphingosine,Phenoxyethanol, Capryl Glycol, Ethylhexylglycerin, and Hexylene glycol.

In some embodiments, the moisturizing composition comprises DI Water,Caprylyl Methicone, PEG-12 Dimethicone, PPG-20 Crosspolymer, AlcoholDenatured, Sodium Hyaluronate, Cetyl hydroxyethylcellulose, Gellan Gum,Glycerin, Pentylene Glycol, Magnesium PCA, Calcium PCA, Sea Salt Fine,Glycerin, Isododecane, Dimethicone, Polysilicone-11, Butylene Glycol,Dimethylacrylamide, Acrylic Acid, Polystyrene Ethyl MethacrylateCopolymer, Coco-Caprylate, Caprate, Decyl Glucoside, HydroxyethylAcrylate, Sodium Acryloyldimethyl Taurate Copolymer, Isohexadecane,Polysorbate 60, Pentylene Glycol, Phenoxyethanol, Capryl Glycol,Ethylhexylglycerin, and Hexylene Glycol.

In some embodiments, the moisturizing composition comprises DI Water,Caprylyl Methicone, PEG-12 Dimethicone, PPG-20 Crosspolymer, AlcoholDenatured, Gellan Gum, Pyrus Malus (Apple) Fruit Extract, Adenosine,Magnesium PCA, Calcium PCA, Sodium benzoate, Sea Salt Fine,Phosphatidylglycerol, Ceteareth-25, Cetyl Alcohol, Behenic Acid,Cholesterol, Ceramide NP, Ceramide NS, Ceramide EOS, Ceramide EOP,Ceramide AP, Caprooyl Phytosphingosine, Caprooyl Sphingosine, Glycerin,Sodium Hyaluronate Crosspolymer, Cetyl hydroxyethylcellulose, SodiumPolyglutamate, Isododecane, Dimethicone, Polysilicone-11, ButyleneGlycol, Dimethylacrylamide, Acrylic Acid, Polystyrene Ethyl MethacrylateCopolymer, Coco-Caprylate, Caprate, Decyl Glucoside, HydroxyethylAcrylate, Sodium Acryloyldimethyl Taurate Copolymer, Isohexadecane,Polysorbate 60, Pentylene Glycol, Phenoxyethanol, Capryl Glycol,Ethylhexylglycerin, and Hexylene Glycol.

In some embodiments, the IPN moisturizing composition is not asemi-interpenetrating polymer network. In some embodiments, the IPNmoisturizing composition is not a sequential interpenetrating polymernetwork. In some embodiments, the IPN moisturizing composition is not asequential semi-interpenetrating polymer network.

The moisturizing compositions of the present invention and/or for use inthe methods of use, and/or methods of making embodied herein may beformulated for cosmetic and dermatological uses. In some embodiments,the moisturizing compositions of the present invention and/or for use inthe methods of use, and/or methods of making embodied herein may beformulated for topical cosmetic and topical dermatological uses. In someembodiments, the compositions of the present invention and/or for use inthe methods of use, and/or methods of making embodied herein may beformulated for topical administration. In some embodiments, themoisturizing compositions described herein may be formulated as creams,serums, milks, lotions, salves, oils, butters, gels, balms or anycombination thereof.

In some embodiments, the moisturizing formulations described herein maybe useful for promoting the exfoliation of dry skin, promoting thedigestion of desmosomes, normalizing cell maturation, or any combinationthereof.

In embodiments described herein, the method of treating dry skincomprises administering a moisturizing composition resulting inimprovement in water retention and hydration of the skin.

In embodiments described herein, the method of treating dry skincomprises administering a moisturizing composition resulting in aself-adjusting moisture level unique to each individual.

In embodiments described herein, the method of treating dry skincomprises administering a moisturizing composition resulting in theimprovement of the skin selected from the group consisting of radiance,fine lines, and overall dryness. Radiance is assessed as the reflectionof light, e.g. shine. In embodiments described herein, the method oftreating dry skin comprises administering a moisturizing compositionresulting in diffuse reflectance and plumping of the skin.

In embodiments described herein, the method of treating dry skincomprises administering a moisturizing composition resulting in animprovement in the moisture content in the stratum corneum. In certainembodiments, the improvement in moisture content in the stratum corneumcan be measured using 2 different techniques. The first technique usesthe Corneometer to measure the capacitance of the surface of the skin,this technique allows for a measurement of the water content of thesuperficial epidermal layers down to a depth of about 0.1 mm. The secondtechnique uses the SKICON to measure the conductance of the surface ofthe skin and the flow of electrons traveling down the surface of theskin.

In embodiments described herein, the method of treating dry skincomprises administering a moisturizing composition resulting in adecrease in the rate of transepidermal water loss (TEWL). TEWL can bemeasured using a Tewameter, the measurement is taken on the skin toassess passive water transport through the stratum corneum. Themeasurement of water evaporation is based on the diffusion principle inan open chamber, and the density gradient is measured indirectly by 2pairs of sensors located inside the hollow cylinder probe. Data areanalyzed by a microprocessor and reported in g/m2/h. A decrease in TEWLvalues reflects an improvement in the barrier properties of the skin andtreatment of dry skin.

In embodiments described herein, the method of treating dry skincomprises administering a moisturizing composition resulting in theimprovement of the viscoelastic properties of the skin selected from thegroup consisting of extensibility, resiliency, pure elasticity,biological elasticity and combinations thereof. In some embodiments, theviscoelastic properties can be measured using a Cutometer.

In embodiments described herein, the method of treating dry skincomprises administering a moisturizing composition resulting in theimprovement of a subject's rating of skin attributes selected from thegroup consisting of moisturization, fine lines, radiance, suppleness,softness, smoothness, bouncy skin, dryness, overall appearance, overallcomfort, tightness, firmness, plumpness, firmness, youthfulness andcombinations thereof.

In some embodiments, the moisturizing formulations described herein maybe useful for modulating keratinocyte function, normalizing keratinocytedifferentiation, normalizing keratinocyte proliferation, modulatingphosphatidylglycerol content of keratinocytes, or any combinationthereof. Without wishing to be bound by theory, keratinocytes play a keyrole in the maintenance of healthy skin. The skin is the largest organof the body and is composed of the epidermis and dermis. The mostimportant function of the skin is to provide a physical and waterpermeability barrier. The epidermis is a continuously regeneratingtissue, which differentiates to produce a mechanical and waterpermeability barrier. This barrier is established in the epidermis by aprecisely regulated keratinocyte differentiation program that results indistinct epidermal layers. The structure of the epidermis is maintainedby a finely tuned balance between keratinocyte proliferation anddifferentiation, which results in a multilayer structure consisting ofbasal, spinous, granular, and cornified layers. The innermost basallayer, which is in contact with the basement membrane, is composed of asingle layer of undifferentiated keratinocytes with proliferativepotential. The spinous layer consists of non-proliferating keratinocytesin an early differentiation stage with progressive maturation as thecells move from suprabasal layers outward. Spinous differentiation isfollowed by late differentiation in the granular layer and terminaldifferentiation in the outermost cornified layer. Once committed todifferentiation, the cells in the basal layer lose their proliferativepotential and move toward the terminally differentiated cornified layer.Precise regulation of differentiation in the epidermis is crucial forproper stratification and barrier formation to occur. Epidermalhomeostasis is maintained in part by orchestrating the correctexpression of genes in keratinocytes at each stage of differentiation.Alterations in this differentiation program can result in skindisorders, such as psoriasis, eczema, atopic dermatitis, skin cancers,such as squamous and basal cell carcinoma, and other conditions of theskin characterized by unregulated cell division. Thus, any upset in thebalance of skin cell proliferation and differentiation signals canresult in various disorders or other undesirable skin conditions. Whilean over-stimulation of keratinocyte proliferation may lead tohyperproliferative skin conditions, such as those mentioned above (i.e.psoriasis and various non-melanoma skin cancers), under-stimulation ofkeratinocyte proliferation may result in insufficient growth, such asthat characterized by aging skin (skin cell senescence) or skin that hasbeen damaged.

In some embodiments, the moisturizing compositions described herein maybe useful for modulating and/or improving the moisture content of theskin, promoting the retention of long lasting hydration in the skin,increasing skin moisture, improving skin water balance, increasing skinhydration, decreasing transepidermal water loss, reducing evaporation ofwater from the skin, or any combination thereof. In some embodiments,the moisturizing compositions described herein may be useful for methodsof treating and/or preventing dry and/or irritated skin. In someembodiments, the moisturizing compositions described herein may beuseful for defending against, and reducing visible signs of aging fornoticeably firmer, smoother, and flawless looking skin. In someembodiments, the moisturizing compositions described herein may beuseful to erase the appearance of premature aging, including brownspots, dullness and discoloration. In some embodiments, the moisturizingcompositions described herein may be useful to visibly brighten theskin. In some embodiments, the moisturizing compositions describedherein may be useful to reduce the appearance of fine lines andwrinkles. In some embodiments, the moisturizing compositions describedherein may be useful to creating a radiant complexion. In someembodiments, the moisturizing compositions described herein may beuseful to shield the skin again biological and environmental aggressorsassociated with dry, irritated and sensitive skin. In some embodiments,the moisturizing compositions described herein may be useful to help theskin retain moisture and remain comfortable when challenged by climateand other environmental aggressors. In some embodiments, themoisturizing compositions described herein may be useful to rehydratethe skin. In some embodiments, the moisturizing compositions describedherein may be useful to repair, renew, and/or enhance the skin's naturalmoisture barrier.

Embodiments, herein are directed to methods of promoting the exfoliationof dry skin, promoting the digestion of desmosomes, normalizing cellmaturation, or any combination thereof, comprising administering amoisturizing composition comprising: an interpenetrating polymer networkmade up of a crosslinked polypeptide or polysaccharide; a branchedpolymer with a hydrophobic modification; and a linear polypeptide orpolysaccharide. Embodiments herein are directed to methods of promotingthe exfoliation of dry skin, promoting the digestion of desmosomes,normalizing cell maturation, or any combination thereof, comprisingadministering a moisturizing composition consisting essentially of: aninterpenetrating polymer network made up of a crosslinked polypeptide orpolysaccharide; a branched polymer with a hydrophobic modification; anda linear polypeptide or polysaccharide. Embodiments herein are directedto methods of promoting the exfoliation of dry skin, promoting thedigestion of desmosomes, normalizing cell maturation, or any combinationthereof, comprising administering a moisturizing composition consistingof: an interpenetrating polymer network made up of a crosslinkedpolypeptide or polysaccharide; a branched polymer with a hydrophobicmodification; and a linear polypeptide or polysaccharide.

Embodiments, herein are directed to methods of modulating keratinocytefunction, normalizing keratinocyte differentiation, normalizingkeratinocyte proliferation, modulating phosphatidylglycerol content ofkeratinocytes, or any combination thereof, comprising administering amoisturizing composition comprising: an interpenetrating polymer networkmade up of a crosslinked polypeptide or polysaccharide; a branchedpolymer with a hydrophobic modification; and a linear polypeptide orpolysaccharide. Embodiments herein are directed to methods of modulatingkeratinocyte function, normalizing keratinocyte differentiation,normalizing keratinocyte proliferation, modulating phosphatidylglycerolcontent of keratinocytes, or any combination thereof, comprisingadministering a moisturizing composition consisting essentially of: aninterpenetrating polymer network made up of a crosslinked polypeptide orpolysaccharide; a branched polymer with a hydrophobic modification; anda linear polypeptide or polysaccharide. Embodiments herein are directedto methods of modulating keratinocyte function, normalizing keratinocytedifferentiation, normalizing keratinocyte proliferation, modulatingphosphatidylglycerol content of keratinocytes, or any combinationthereof, comprising administering a moisturizing composition consistingof: an interpenetrating polymer network made up of a crosslinkedpolypeptide or polysaccharide; a branched polymer with a hydrophobicmodification; and a linear polypeptide or polysaccharide.

Embodiments, herein are directed to methods of modulating and/orimproving the moisture content of the skin, promoting the retention oflong lasting hydration in the skin, increasing skin moisture, improvingskin water balance, increasing skin hydration, decreasing transepidermalwater loss, reducing evaporation of water from the skin, shield the skinagainst biological and environmental aggressors associated with dry,irritated and sensitive skin, help the skin retain moisture and remaincomfortable when challenged by climate and other environmentalaggressors, or any combination thereof, comprising administering amoisturizing composition comprising: an interpenetrating polymer networkmade up of a crosslinked polypeptide or polysaccharide; a branchedpolymer with a hydrophobic modification; and a linear polypeptide orpolysaccharide. Embodiments herein are directed to methods of modulatingand/or improving the moisture content of the skin, promoting theretention of long lasting hydration in the skin, increasing skinmoisture, improving skin water balance, increasing skin hydration,decreasing transepidermal water loss, reducing evaporation of water fromthe skin, shield the skin against biological and environmentalaggressors associated with dry, irritated and sensitive skin, help theskin retain moisture and remain comfortable when challenged by climateand other environmental aggressors, or any combination thereof,comprising administering a moisturizing composition consistingessentially of: an interpenetrating polymer network made up of acrosslinked polypeptide or polysaccharide; a branched polymer with ahydrophobic modification; and a linear polypeptide or polysaccharide.Embodiments herein are directed to methods of modulating and/orimproving the moisture content of the skin, promoting the retention oflong lasting hydration in the skin, increasing skin moisture, improvingskin water balance, increasing skin hydration, decreasing transepidermalwater loss, reducing evaporation of water from the skin, shield the skinagainst biological and environmental aggressors associated with dry,irritated and sensitive skin, help the skin retain moisture and remaincomfortable when challenged by climate and other environmentalaggressors, or any combination thereof, comprising administering amoisturizing composition consisting of: an interpenetrating polymernetwork made up of a crosslinked polypeptide or polysaccharide; abranched polymer with a hydrophobic modification; and a linearpolypeptide or polysaccharide.

Embodiments, herein are directed to methods of defending against, andreducing visible signs of aging for noticeably firmer, smoother, andflawless looking skin, erasing the appearance of premature aging,including brown spots, dullness and discoloration, visibly brighteningthe skin, reduce the appearance of fine lines and wrinkles, creating aradiant complexion, or any combination thereof, comprising administeringa moisturizing composition consisting of: an interpenetrating polymernetwork made up of a crosslinked polypeptide or polysaccharide; abranched polymer with a hydrophobic modification; and a linearpolypeptide or polysaccharide. Embodiments, herein are directed tomethods of defending against, and reducing visible signs of aging fornoticeably firmer, smoother, and flawless looking skin, erasing theappearance of premature aging, including brown spots, dullness anddiscoloration, visibly brightening the skin, reduce the appearance offine lines and wrinkles, creating a radiant complexion, or anycombination thereof, comprising administering a moisturizing compositionconsisting essentially of: an interpenetrating polymer network made upof a crosslinked polypeptide or polysaccharide; a branched polymer witha hydrophobic modification; and a linear polypeptide or polysaccharide.Embodiments, herein are directed to methods of defending against, andreducing visible signs of aging for noticeably firmer, smoother, andflawless looking skin, erasing the appearance of premature aging,including brown spots, dullness and discoloration, visibly brighteningthe skin, reduce the appearance of fine lines and wrinkles, creating aradiant complexion, or any combination thereof, comprising administeringa moisturizing composition comprising: an interpenetrating polymernetwork made up of a crosslinked polypeptide or polysaccharide; abranched polymer with a hydrophobic modification; and a linearpolypeptide or polysaccharide. Embodiments herein are directed tomethods of treating and/or preventing dry and/or irritated skincomprising administering a moisturizing composition comprising: aninterpenetrating polymer network made up of a crosslinked polypeptide orpolysaccharide; a branched polymer with a hydrophobic modification; anda linear polypeptide or polysaccharide. Embodiments herein are directedto methods of treating dry and/or irritated skin comprisingadministering a moisturizing composition consisting essentially of: aninterpenetrating polymer network made up of a crosslinked polypeptide orpolysaccharide; a branched polymer with a hydrophobic modification; anda linear polypeptide or polysaccharide. Embodiments herein are directedto methods of treating dry and/or irritated skin comprisingadministering a moisturizing composition consisting of: aninterpenetrating polymer network made up of a crosslinked polypeptide orpolysaccharide; a branched polymer with a hydrophobic modification; anda linear polypeptide or polysaccharide.

Embodiments herein are directed to a method for delivering an activeingredient or drug comprising administering an interpenetrating polymernetwork made up of a crosslinked polypeptide or polysaccharide; abranched polymer with a hydrophobic modification; a linear polypeptideor polysaccharide; and an active ingredient; wherein the crosslinkedpolypeptide or polysaccharide entraps the interlaced branched polymerwith a hydrophobic modification, the linear polypeptide orpolysaccharide, and the active ingredient or drug to form theinterpenetrating polymer network. In some embodiments, the activeingredient or drug is selected from the group consisting of skintreatments, skin protectants, acne treatments, wrinkle treatments,exfoliating acids, skin brightening agents, and anti-inflammatoryagents, In some embodiments, the acne treatment is selected from thegroup consisting of benzoyl peroxide, salicylic acid, willowbarkextract, poly hydroxyacid, tannic acid, hydroxybenzoic acid, junipericacid, tartaric acid, glycolic acid, lactic acid, and citric acid. Insome embodiments, the wrinkle treatment is selected from the groupconsisting of retinol, antioxidants, vitamin A, retinoid, tretinoin, andtazarotene. In some embodiments, the anti-inflammatory agent is selectedfrom the group consisting of ibuprofen, diclofenac, felbinac,ketoprofen, and piroxicam. In some embodiments, the skin protectant isglycerin. In some embodiments, the exfoliating acid is selected from thegroup consisting of glycolic acid, alpha hydroxyl acid (AHA), andpolyhydroxyacid. In some embodiments, the skin brightening agent isselected from the group consisting of hydroquinone, hexyl resorcinol,and phenylethyl resorcinol.

In some embodiments, the compositions for use in the methods describedherein are an interpenetrating polymer network comprising a crosslinkedpolypeptide or polysaccharide; a branched polymer with a hydrophobicmodification; and a linear polypeptide or polysaccharide, wherein thecrosslinked polypeptide or polysaccharide entraps the interlacedbranched polymer with a hydrophobic modification and the linearpolypeptide or polysaccharide to form the interpenetrating polymernetwork. In some embodiments, the polysaccharide capable ofcrosslinking, the branched polymer with a hydrophobic modification andthe linear polypeptide or polysaccharide form an interpenetratingpolymer network.

In some embodiments the crosslinked polypeptide or polysaccharide isselected from the group consisting of crosslinked gellan gum,crosslinked carrageenan, crosslinked chitosan crosslinked xanthan gum,sodium polyglutamate crosspolymer, polydextrose, and combinationsthereof. In some embodiments, the crosslinked polypeptide orpolysaccharide is crosslinked gellan gum.

In some embodiments the branched polymer with a hydrophobic modificationis selected from the group consisting of hydrophobically modifiedhydroxypropylmethylcellulose, hydrophobically modified cetyl hydroxypropyl methyl cellulose, hydrophobically modified sodium acetylhyaluronate, hydrophobically modified cetyl hydroxyethylcellulose,hydrophobically modified starch, hydrophobically modifiedcarboxymethylchitosan, and combinations thereof. In some embodiments,the branched polymer with a hydrophobic modification is hydrophobicallymodified cetyl hydroxyethylcellulose.

In some embodiments, the linear polypeptide or polysaccharide isselected from the group consisting of gellan gum, carrageenan, xanthangum, biosaccharide gum-1, sclerotium gum, pectin, pullulan, guar gum,gum arabic, chondroitin, sulfate, alginic acid, sodium hyaluronate,hydrolyzed hyaluronic acid sodium polyglutamate, chitin, chitosan,starch, and combinations thereof. In some embodiments, the linearpolypeptide or polysaccharide is sodium hyaluronate.

In some embodiments the crosslinked polypeptide or polysaccharide,branched polymer with a hydrophobic modification; and linear polypeptideor polysaccharide comprise from about 0.01% to about 5% of thecomposition by weight.

In some embodiments the moisturizing composition further comprises amono-, or di-valent ion. In some embodiments the mono-, or di-valent ionis selected from the group consisting of 2-Pyrrolidone-5-Carboxylic Acidand related salts, calcium PCA, sodium PCA, zinc PCA, magnesium PCA, seasalt, inorganic salts of citric acid, inorganic salts of lactic acid,calcium ascorbate, magnesium ascorbate, calcium oxide, calcium benzoate,calcium sorbate, calcium aspartate, magnesium carbonate, magnesiumchloride, magnesium nitrate, and any combination thereof. In someembodiments the mono-, or di-valent ion includes calcium PCA, magnesiumPCA, and sea salt. Without wishing to be bound by theory, mono- anddi-valent salts such as, but not limited to calcium PCA and MagnesiumPCA can facilitate the cross-linking of a linear polypeptide orpolysaccharide such as but not limited to gellan gum into aninterpenetrating polymer network. In some embodiments, the mono-, ordi-valent ion comprises between about 0.01% to about 5% of thecomposition by weight.

In some embodiments, the moisturizing composition further comprises atleast one humectant. In some embodiments, the at least one skinconditioning/non polymeric humectant is selected from the groupconsisting of glycerin, diglycerin, betaine, diols, propylene glycol,butylene glycol, pentylene glycol, propanediol, 1,2-hexanediol,D-ribose, glucose, sorbitol, dextrose, urea, 2-Pyrrolidone-5-CarboxylicAcid and related salts, sea salt, inorganic salts of citric acid,inorganic salts of lactic acid, ectoin, lactic acid, betaine, glycolicacid, lactobionic acid, and any combination thereof. In someembodiments, the humectant includes glycerin and pentylene glycol. Insome embodiments, the skin conditioning/non polymeric humectantcomprises at least about 30% of the composition by weight. In someembodiments, the at least one humectant comprises between about 25% toabout 80% of the composition by weight.

In some embodiments, the moisturizing composition further comprises anactive agent. In some embodiments, the active agent is selected from thegroup consisting of glycerin, diglycerin, betaine, diols, propyleneglycol, butylene glycol, pentylene glycol, propanediol, 1,2-hexanediol,D-ribose, glucose, sorbitol, dextrose, urea, 2-Pyrrolidone-5-CarboxylicAcid and related salts, sea salt, inorganic salts of citric acid,inorganic salts of lactic acid, ectoin, lactic acid, betaine, glycolicacid, lactobionic acid, and any combination thereof. In someembodiments, the active agent is a cell cycle modulator. In someembodiments, the cell cycle modulator is selected from the groupconsisting of phosphatidylglycerol, calcium PCA, Lysolecithin, and anycombination thereof. Without wishing to be bound by theory, increasingmoisture content at the skin's surface may not be enough as a long termstrategy for combating the effects of dry skin. It is believed that thekeratinocyte cell cycle has implications on dry skin. In biopsy studies,epidermal under-differentiation appears to be linked with dry skin inboth young and old populations. In some embodiments, other cellularmodulations can also be considered such as gene expression manipulationof AQP3 for improving skin hydration via cellular glycerol/waterchannels.

In some embodiments, the moisturizing composition further comprises akeratinocyte differentiation promoting agent. In some embodiments, thekeratinocyte differentiation promoting agent is selected from the groupconsisting of phosphatidylglycerol, an organic salt ofglycerophosphoinositol, calcium PCA, calcium lactate, calcium citrate orother forms of soluble calcium, hydroxyapatite, cortisone, ceramides,ergocalciferol, cholecalciferol, sphingolipids, and any combinationthereof.

In some embodiments, the moisturizing compositions described herein mayfurther comprise a preservative system. In some embodiments, thepreservative system may comprise phenoxyethanol, capryl glycol,ethylhexylglycerin, hexylene glycol, sodium benzoate, potassium sorbate,methyl paraben, gluconolactone, lactic acid, sorbic acid, glycerylcaprylate, glyceryl undecylenate, ethanol, chlorphenesin, salicylic acidor any combination thereof. In some embodiments, the preservative systemmay comprise phenoxyethanol and capryl glycol and ethylhexylglycerin andhexylene glycol. In yet other embodiments, the preservative system maycomprise glyceryl caprylate and glyceryl undecylenate.

In some embodiments, the moisturizing compositions described herein mayfurther comprise caprylyl methicone-cosmetic silicone, PEG-12dimethicone/PPG-20 Crosspolymer, alcohol denatured, isododecane,polysilicone-11, Dimethylacrylamide/Acrylic Acid/Polystyrene EthylMethacrylate Copolymer, coco-caprylate/Caprate, decyl glucoside,Hydroxyethyl Acrylate/Sodium Acryloyldimethyl Taurate Copolymer,Isohexadecane, and polysorbate 60.

Embodiments herein are directed to a method of producing ainterpenetrating polymer network moisturizing composition, the methodcomprising: dispersing a non-crosslinked polypeptide or polysaccharidecapable of crosslinking in water to form a first phase; combining alinear polypeptide or polysaccharide and a branched polymer with ahydrophobic modification with a humectant to form a second phase;combining the first and second phases to form a third phase ofuncrosslinked interlaced polymers, polypeptides, or polysaccharides;adding a mono-valent ion, di-valent ion or a combination thereof to thethird phase to crosslink one or more polypeptide, polymer, orpolysaccharide to form an interpenetrating polymer network moisturizingcomposition. Without wishing to be bound by theory, combining the firstphase with the second phase results in the formation of an interlacedpolymer network but it is not until the addition of the crosslinkingagent that the non-crosslinked polypeptide or polysaccharide capable ofcrosslinking actually becomes crosslinked to form an interpenetratingpolymer network. This interpenetrating polymer network is made up of acrosslinked polypeptide or polysaccharide in a three dimensionalstructure; a branched polymer with a hydrophobic modification; and alinear polypeptide or polysaccharide, wherein the crosslinkedpolypeptide or polysaccharide entraps the interlaced branched polymerwith a hydrophobic modification and the linear polypeptide orpolysaccharide.

In some embodiments, the linear polypeptide or polysaccharide is a isselected from the group consisting of gellan gum, carrageenan, xanthangum, biosaccharide gum-1, sclerotium gum, pectin, pullulan, guar gum,gum arabic, chondroitin, sulfate, alginic acid, sodium hyaluronate,hydrolyzed hyaluronic acid sodium polyglutamate, chitin, chitosan,starch, and combinations thereof.

In some embodiments, the non-crosslinked polypeptide or polysaccharidecapable of crosslinking is selected from the group consisting of gellangum, carrageenan, chitosan xanthan gum, sodium polyglutamatecrosspolymer, polydextrose, and combinations thereof. In someembodiments, the non-crosslinked polypeptide or polysaccharide capableof crosslinking is gellan gum. In some embodiments, the gellan gum isselected from the group consisting of Kelcogel CG-HA, Kelcogel CG-LA,and any combination thereof. In some embodiments, the gellan gumcomprises a mixture of Kelcogel CG-HA, and Kelcogel CG-LA. In someembodiments, dispersing the gellan gum in water to form a first phasefurther comprises pre-blending at least two gellan gum powders. In someembodiments, the at least two gellan gum powders are selected from thegroup consisting of Kelcogel CG-HA, Kelcogel CG-LA, and any combinationthereof. Some embodiments further comprise heating the first phase toabout 75° C. Some embodiments further comprise homogenizing the firstphase.

In some embodiments, the first and second phases with at least onecrosslinking agent in water to form the interpenetrating polymer networkmoisturizing composition further comprises the addition of USP Glycerin,Pyrus Malus (Apple) Fruit Extract, Glycerin, Pentylene Glycol,Bis-PEG-12 Dimethicone, Phenoxyethanol, capryl glycol,ethylhexylglycerin, hexylene glycol, or any combination thereof.

In some embodiments, the step of dispersing a non-crosslinkedpolypeptide or polysaccharide capable of crosslinking in water to form afirst phase is heated to about 75° C. to about 90° C. In someembodiments, the non-crosslinked polypeptide or polysaccharide capableof crosslinking is a mixture of two different polypeptide orpolysaccharide. In a preferred embodiment, the non-crosslinkedpolypeptide or polysaccharide capable of crosslinking is a mixture ofLow Acyl (LA) gellan gum and High Acyl (HA) gellan gum. Without wishingto be bound by theory, the non-crosslinked polypeptide or polysaccharidecapable of crosslinking unravels and becomes soluble with no organizedstructure once it is placed in water.

In some embodiments, the at least one crosslinking agent is selectedfrom group consisting of 2-Pyrrolidone-5-Carboxylic Acid and relatedsalts calcium PCA, sodium PCA, zinc PCA, magnesium PCA, sea salt,inorganic salts of citric acid, inorganic salts of lactic acid, calciumascorbate, magnesium ascorbate, calcium oxide, calcium benzoate, calciumsorbate, calcium aspartate, magnesium carbonate, magnesium chloride,magnesium nitrate, and any combination thereof. In some embodiments,combining the first and second phases with at least one crosslinkingagent in water to form the moisturizing composition further comprisesadding adenosine, sodium benzoate, ESP sea salt fine or any combinationthereof.

In some embodiments, the step of combining a linear polypeptide orpolysaccharide and a branched polymer with a hydrophobic modificationwith a humectant to form a second phase further comprises dispersingpre-bended powdered ingredients into a pre-mixed mixture of liquidcomponents to form the second phase, and heating the second phase toabout 75° C. to about 80° C. In a preferred embodiment, the linearpolypeptide is sodium hyaluronate and the branched polymer with ahydrophobic modification is hydrophobically modifiedhydroxyethylcellulose, each is combined and swell in the humectant,glycerin. The three components have no three dimensional structure andare heated to between 75° C. and 80° C.

In some embodiments, the step of combining the first and second phasesto form a third phase of uncrosslinked interlaced polymers,polypeptides, or polysaccharides is accomplished by mixing the solutionsto form a uniform thin liquid solution.

In some embodiments, the step of adding a mono-valent ion, di-valent ionor combination thereof to the third phase to crosslink one or morepolypeptide, polymer, or polysaccharide further comprises cooling themixture to about 22° C. to about 40° C. Without wishing to be bound bytheory, the crosslinking of the polypeptide or polysaccharide capable ofcrosslinking begins to form a three dimensional structure immediately.This is visualized as a semi-solid continuous flowable gel. Thecrosslinking process continues until the solution has completely cooledto at least 40° C. The resulting 3 dimensional gel structure entraps thelinear polypeptide or polysaccharide and a branched polymer with ahydrophobic modification in an uniform distribution as all thecomponents started as fully miscible soluble components when heated toabout 75° C.-80° C. The resulting composition is the interpenetratingpolymer network described herein.

Some embodiments further comprise heating the interpenetrating polymernetwork moisturizing composition to between about 65° C. and about 80°C. Some embodiments, further comprise cooling the interpenetratingpolymer network moisturizing composition to about 40° C. Someembodiments further comprise cooling the interpenetrating polymernetwork moisturizing composition to room temperature.

Some embodiments further comprise homogenizing the interpenetratingpolymer network moisturizing composition until it is smooth andhomogenous.

In some embodiments, combining the first and second phases with at leastone crosslinking agent in water to form the interpenetrating polymernetwork moisturizing composition further comprises adding an activeagent. In some embodiments, the active agent is selected from the groupconsisting of ceramide, water, humectants, natural moisturizing factors,osmolytes, bio-active hydrators Glycerin; Behenic Acid, Cholesterol,Ceramide NP, Ceramide NS, Ceramide EOS, Ceramide EOP, Ceramide AP,Caprooyl Phytosphingosine, Caprooyl Sphingosine, calcium salts,hydroxyapatite, palmitic acid, adenosine, peptides, and any combinationthereof.

In some embodiments, combining the first and second phases with at leastone crosslinking agent in water to form the interpenetrating polymernetwork moisturizing composition further comprises adding a keratinocytedifferentiation promoting agent. In some embodiments, the keratinocytedifferentiation promoting agent is selected from the group consisting ofphosphatidylglycerol, an organic salt of glycerophosphoinositol, calciumPCA, calcium lactate, calcium citrate or other forms of soluble calcium,hydroxyapatite, cortisone, ceramides, ergocalciferol, cholecalciferol,sphingolipids, and any combination thereof.

In some embodiments, the humectant is selected from the group consistinglactic acid, glycerin, phosphatidylglycerol, ceteareth-25, glycerin,cetyl alcohol; behenic Acid, cholesterol, ceramide NP, ceramide NS,ceramide EOS, ceramide EOP, ceramide AP, caprooyl phytosphingosine,caprooyl sphingosine and any combination thereof.

In some embodiments, combining the first and second phases with at leastone crosslinking agent in water to form the interpenetrating polymernetwork moisturizing composition further comprises adding furthercomprises a preservative system. In some embodiments, the preservativesystem may comprise phenoxyethanol, capryl glycol, ethylhexylglycerin,hexylene glycol, sodium benzoate, potassium sorbate, methyl paraben,gluconolactone, lactic acid, sorbic acid, glyceryl caprylate, glycerylundecylenate, ethanol, chlorphenesin, salicylic acid or any combinationthereof. In some embodiments, the preservative system may comprisephenoxyethanol and capryl glycol and ethylhexylglycerin and hexyleneglycol. In yet other embodiments, the preservative system may compriseglyceryl caprylate and glyceryl undecylenate.

In some embodiments, the moisturizing compositions described herein mayfurther comprise caprylyl methicone-cosmetic silicone, PEG-12dimethicone/PPG-20 Crosspolymer, alcohol denatured, isododecane,polysilicone-11, Dimethylacrylamide/Acrylic Acid/Polystyrene EthylMethacrylate Copolymer, coco-caprylate/Caprate, decyl glucoside,Hydroxyethyl Acrylate/Sodium Acryloyldimethyl Taurate Copolymer,Isohexadecane, and polysorbate 60.

Some embodiments are directed to an interpenetrating polymer networkmoisturizing compositions formed by the methods described herein.

In some embodiments, the moisturizing compositions described herein mayinclude a solvent. In some embodiments, the solvent is water.

Humectants for use in the compositions and methods described hereininclude, but are not limited to pyrus malus (apple) fruit extract,pentylene glycol, magnesium PCA (Mg²⁺ crosslinks gellan gum; humectantnatural moisturizing factor, balances calcium activity), calcium PCA(Ca²⁺ crosslinks gellan gum; humectant natural moisturizing factor,calcium support differentiation), sea salt (humectant electrolyte breaksdown thickener in Redefine creams), glycerin (humectant OTC skinprotectant at 30%, supports desquamation via desmosome digestion),Phosphatidylglycerol (humectant carrier expresses AQ3, delivers glycerininto skin, differentiates keratinocytes), Bis-PEG-12 Dimethicone(sensory modifier with humectant properties) sodium benzoate(preservative with humectant properties), phenoxyethanol (and) caprylglycol (and) ethylhexylglycerin (and) hexylene glycol (preservativeswith humectant properties),

In some embodiments, agents that support and/or mimic the skin's naturalbarrier function and/or support differentiation can be used in thecompositions and methods described herein. Such agents include, but arenot limited to ceteareth-25, glycerin, cetyl alcohol, behenic acid,cholesterol, ceramide NP, ceramide NS, ceramide EOS, ceramide EOP,ceramide AP, caprooyl phytosphingosine, and caprooyl sphingosine.

In some embodiments, anti-aging and skin conditioning agents can be usedin the compositions and methods described herein. Such agents include,but are not limited to adenosine

In some embodiments, the moisturizing compositions described herein mayinclude a moisturizer. In some embodiments, moisturizer include, but arenot limited to lactic acid.

It is also known in the art that the active ingredients may be containedin such compositions with cosmetically and/or pharmaceuticallyacceptable diluents, fillers, disintegrants, binders, lubricants,surfactants, hydrophobic vehicles, water-soluble vehicles, emulsifiers,buffers, humectants, moisturizers, solubilizers, preservatives and thelike. The means and methods for administration are known in the art andan artisan can refer to various pharmacologic references for guidance.For example, Modern Pharmaceutics, Banker & Rhodes, Marcel Dekker, Inc.(1979); and Goodman & Gilman's The Pharmaceutical Basis of Therapeutics,6th Edition, MacMillan Publishing Co., New York (1980) can be consulted.

The cosmetic compositions described herein may be prepared, packaged, orsold in bulk as a single unit dose or as multiple unit doses and may beadministered in the conventional manner by any route where they areactive. For example, the compositions may be administered transdermally,subcutaneously, topically, and transdermal forms such as patches andcreams. Specific modes of administration will depend on the indication.The selection of the specific route of administration and the doseregimen may be adjusted or titrated by the artisan according to knownmethods in order to obtain the optimal clinical response. All of themethods described herein may be carried out by administering themoisturizing compositions described herein by any such route foradministration described herein. Additionally, the moisturizingcompositions disclosed herein may be delivered by using any such routeof administration for all of the dosage regimens described herein. Thecompositions and amounts of non-active ingredients in such a compositionmay depend on the amount of the active ingredient, and on the size andshape of the tablet or capsule. Such parameters may be readilyappreciated and understood by one of skill in the art.

Embodiments of the invention are not limited to any particular agentencompassed by the classes of agents described above, and any agent thatfalls within any of these categories may be utilized in embodiments ofthe invention. Non-limiting examples of such agents are provided forclarity. Any of the secondary agents described above may be useful inembodiments of the invention.

Unless otherwise indicated, all numbers expressing quantities ofingredients, properties such as molecular weight, reaction conditions,and so forth used in the specification and claims are to be understoodas being modified in all instances by the term “about.” Accordingly,unless indicated to the contrary, the numerical parameters set forth inthe specification and attached claims are approximations that may varydepending upon the desired properties sought to be obtained by thepresent invention. At the very least, and not as an attempt to limit theapplication of the doctrine of equivalents to the scope of the claims,each numerical parameter should at least be construed in light of thenumber of reported significant digits and by applying ordinary roundingtechniques. Notwithstanding that the numerical ranges and parameterssetting forth the broad scope of the invention are approximations, thenumerical values set forth in the specific examples are reported asprecisely as possible. Any numerical value, however, inherently containscertain errors necessarily resulting from the standard deviation foundin their respective testing measurements.

Recitation of ranges of values herein is merely intended to serve as ashorthand method of referring individually to each separate valuefalling within the range. Unless otherwise indicated herein, eachindividual value is incorporated into the specification as if it wereindividually recited herein. All methods described herein can beperformed in any suitable order unless otherwise indicated herein orotherwise clearly contradicted by context. The use of any and allexamples, or exemplary language (e.g., “such as”) provided herein isintended merely to better illuminate the invention and does not pose alimitation on the scope of the invention otherwise claimed. No languagein the specification should be construed as indicating any non-claimedelement essential to the practice of the invention.

Groupings of alternative elements or embodiments of the inventiondisclosed herein are not to be construed as limitations. Each groupmember may be referred to and claimed individually or in any combinationwith other members of the group or other elements found herein. It isanticipated that one or more members of a group may be included in, ordeleted from, a group for reasons of convenience and/or patentability.When any such inclusion or deletion occurs, the specification is deemedto contain the group as modified thus fulfilling the written descriptionof all Markush groups used in the appended claims.

Certain embodiments of this invention are described herein, includingthe best mode known to the inventors for carrying out the invention. Ofcourse, variations on these described embodiments will become apparentto those of ordinary skill in the art upon reading the foregoingdescription. The inventor expects skilled artisans to employ suchvariations as appropriate, and the inventors intend for the invention tobe practiced otherwise than specifically described herein. Accordingly,this invention includes all modifications and equivalents of the subjectmatter recited in the claims appended hereto as permitted by applicablelaw. Moreover, any combination of the above-described elements in allpossible variations thereof is encompassed by the invention unlessotherwise indicated herein or otherwise clearly contradicted by context.

Specific embodiments disclosed herein may be further limited in theclaims using “consisting of” or “consisting essentially of” language,rather than “comprising”. When used in the claims, whether as filed oradded per amendment, the transition term “consisting of” excludes anyelement, step, or ingredient not specified in the claims. The transitionterm “consisting essentially of” limits the scope of a claim to thespecified materials or steps and those that do not materially affect thebasic and novel characteristic(s). Embodiments of the invention soclaimed are inherently or expressly described and enabled herein.

In closing, it is to be understood that the embodiments of the inventiondisclosed herein are illustrative of the principles of the presentinvention. Other modifications that may be employed are within the scopeof the invention. Thus, by way of example, but not of limitation,alternative configurations of the present invention may be utilized inaccordance with the teachings herein. Accordingly, the present inventionis not limited to that precisely as shown and described.

EXAMPLES Example 1—Exemplary Interpenetrating Polymer NetworkMoisturizing Composition (3Dimensional 3Polymer Matrix—3D3P)

Table 1 provides the formulation for an exemplary 3D3P composition.

TABLE 1 3D3P formulation Trade name Supplier INCI % W/W DI Water/Aqua49.83 Kelcogel CG-HA Univar/Kelco Gellan Gum 0.03 CP Kelcogel CG-LAUnivar/Kelco Gellan Gum 0.08 CP USP Glycerin USP Glycerin 27.00Botanimoist AMS Botanigenics Pyrus Malus (Apple) 1.00 Fruit Extract(and) Glycerin Hydrolite 5 Symrise Pentylene Glycol 3.00 Gransil VX-419Grant Bis-PEG-12 3.00 Industries Dimethicone Botanistat PF64Botanigenics Phenoxyethanol (and) 0.70 capryl glycol (and)ethylhexylglycerin (and) hexylene glycol Distinctive Bio Resources ofSodium Hyaluronate 0.12 Sodium Nature Hyaluronate (#10094) Polysurf 67CSAshland Cetyl 0.30 hydroxyethylcellulose DI Water/Aqua 10.00 OriStar ADSOriStar Adenosine 0.04 Magnolidone Solabia Magnesium PCA 0.30 CalcidoneSolabia Calcium PCA 0.30 OriStar Sodium benzoate 0.10 Earth Supplied ESPSea Salt Fine 0.10 Products 90% lactic acid 0.10 (dilute if needed)Distinctive ® Bio- Resources of Glycerin (and) 3.00 Signal Lipid RF-IINature Phosphatidylglycerol (DC4038) Skinmimics ® Evonik Ceteareth-25;Glycerin; 1.00 Cetyl Alcohol; Behenic Acid; Cholesterol; Ceramide NP;Ceramide NS; Ceramide EOS; Ceramide EOP; Ceramide AP; CaprooylPhytosphingosine; Caprooyl Sphingosine 100.00

Example 2—Preparation of the Exemplary Interpenetrating Polymer NetworkMoisturizing Composition

Table 2 provides instructions for preparing an exemplary 3D3Pformulation.

TABLE 2 3D3P preparation Phase Trade name Supplier INCI % W/W A DIWater/Aqua 49.83 A Kelcogel CG-HA Univar/Kelco Gellan Gum 0.03 CP AKelcogel CG-LA Univar/Kelco Gellan Gum 0.08 CP Pre-blend powder, slowlydisperse into water with propeller mixing, heat to 75 C. Start slowhomogenizing at 75 C.. (to produce the First Phase) B USP Glycerin USPGlycerin 27.00 B Botanimoist AMS Botanigenics Pyrus Malus (Apple) 1.00Fruit Extract (and) Glycerin B Hydrolite 5 Symrise Pentylene Glycol 3.00B Gransil VX-419 Grant Bis-PEG-12 3.00 Industries Dimethicone BBotanistat PF64 Botanigenics Phenoxyethanol (and) 0.70 capryl glycol(and) ethylhexylglycerin (and) hexylene glycol B Distinctive BioResources of Sodium Hyaluronate 0.12 Sodium Nature Hyaluronate (#10094)B Polysurf 67CS Ashland Cetyl 0.30 hydroxyethylcellulose Start mixingliquids with propeller, pre-blend powders and slowly disperse intoliquid phase B. Heat to 75 C. under propeller agitation. (to produce theSecond Phase) C DI Water/Aqua 10.00 C OriStar ADS OriStar Adenosine 0.04C Magnolidone Solabia Magnesium PCA 0.30 C Calcidone Solabia Calcium PCA0.30 C OriStar Sodium benzoate 0.10 C Earth Supplied ESP Sea Salt Fine0.10 Products Disperse powders in water until fully dissolved, add heatif required. Add B to A while under slow homogenization. (to produce theThird Phase) Continue homogenization for 10 minutes. Add C to A/B whileunder slow homogenization. Allow to cool to 40 C. under slowhomogenization. D 90% lactic acid 0.10 (dilute if needed) DDistinctive ® Bio- Resources of Glycerin (and) 3.00 Signal Lipid RF-IINature Phosphatidylglycerol (DC4038) D Skinmimics ® Evonik Ceteareth-25;Glycerin; 1.00 Cetyl Alcohol; Behenic Acid; Cholesterol; Ceramide NP;Ceramide NS; Ceramide EOS; Ceramide EOP; Ceramide AP; CaprooylPhytosphingosine; Caprooyl Sphingosine Add D to A/B/C under slowhomogenization allow to cool to RT. Homogenize until product is smoothand consistent. 100.00 pH at RT: 4.44

Example 3-3D-3P Interpenetrating Polymer Network Hydration Scaffold(Dilutable Concentrate)

Below is an example of a 3D-3P Interpenetrating Polymer_NetworkHydration Scaffold (dilutable concentrate) formed using SodiumHyaluronate Crosspolymer, Table 3. The product had a clear homogenousgel with viscoelastic properties. This example likely formed asemi-interpenetrating polymer network. It is likely that all polymersare miscible in solution and form a continuous phase but nothing existsto hold them in place since Sodium Hyaluronate Crosspolymer was alreadycrosslinked prior to mixing the polymers in solution. In comparison 3D3PInterpenetrating Polymer_Network from Example 1 cross-links the gellangum (with calcium and magnesium) after the polymers have interlaced insolution. This cross linking secures a more rigid structure trapping thepolymers together.

TABLE 3 3D-3P Interpenetrating Polymer_Network Hydration Scaffold RawMaterial INCI % W/W Glycerin Glycerin 66.50 Hylasome EG6 SodiumHyaluronate Crosspolymer (and) 30.00 pentylene glycol andethylhexylglycerin Natrosol 330CS Cetyl hydroxyethylcellulose 2.50 TegoCosmo PGA Sodium Polyglutamate 1.00 100.00

A 3D3P (3 dimensional 3 polymer) interpenetrating polymer network (IPN)was assembled by unraveling dry spooled gellan gum in water andintroducing a hydrophobically modified cellulose and a linear sodiumhyaluronate into the gellan gum solution. Once the 3 polymers wereinterlaced divalent magnesium and calcium ions were added in the form ofnatural moisturizing factors (PCA salts) to cross-link the gellan gumforming a gelatinous IPN. The composition contained a blend ofhumectants including about 30% glycerin to attract and bind water inaddition to potentially assisting in normalizing desquamation. Theintroduction of calcium ions in the form a pyroglutamic acid salt alsohad the potential to support barrier homeostasis. This superhumectant3D3P IPN (represented in FIG. 16B) was examined with both in vitro andin vivo techniques to determine the effectiveness in restoring hydrationlevels at the stratum corneum and the capacity of this IPN to attractand bind water molecules.

Example 4—Exemplary Interpenetrating Polymer Network MoisturizingComposition Formulated for Use as a Body Milk

The interpenetrating polymer network moisturizing compositions describedherein (i.e. 3D3P Moisture Essence) can be formulated for use in a bodymilk, Table 4.

TABLE 4 3D3P Moisture Essence in a body milk formulation Phase Tradename Supplier INCI % W/W A USP Glycerin USP Glycerin 5.00 A BarsolvNS-100 Barnet Polyglyceryl-10 Laurate 2.4 Slowly disperse Glycerin intoBarsolv NS-100 with propeller mixing until a homogeneous gel is obtainedB Hydrasynol DOI Sytheon Isosorbide dicaprylate 2.00 B Lipex ShealightAAK Shea Butter Ethyl Esters 5.00 B VOLASIL ® DM-2 Chemtec Dimethicone1.00 B Barsil 2001 Barnet Dimethicone 0.30 Start mixing liquids withpropeller, and slowly disperse into gel phase A. C 3D3P Moisture RFProprietary Blend*RF 3D3P 10.00 Essence Moisture Essence Ingredient DeckC Butylene Glycol Butylene Glycol 3.50 C DI Water/Aqua 64.60 C DowCorning ® EP Dow Dimethicone/Vinyl Dimethicone 3.00 9801 HydroCorning/Nexeo Crosspolymer (and) Silica (and) Cosmetic Powder SolButylene Glycol C SIMULGEL ™ INS Seppic Hydroxyethyl Acrylate/Sodium2.50 100 Acryloyldimethyl Taurate Copolymer (and) Isohexadecane (and)Polysorbate 60 C Botanistat PF64 Botanigenics Phenoxyethanol (and)capryl 0.70 glycol (and) ethylhexylglycerin (and) hexylene glycol Startmixing liquids with propeller, and slowly add Simulgel INS 100 mixinguntil a homogeneous gel is obtained. Disperse into gel phase (A&B) andmixing well.

Example 5—Exemplary Interpenetrating Polymer Network MoisturizingComposition for Use as a Body Serum

The interpenetrating polymer network moisturizing compositions describedherein (i.e. 3D3P Moisture Essence) can be formulated for use in a bodyserum, Table 5.

TABLE 5 3D3P Moisture Essence in a body serum formulation Phase Tradename Supplier INCI % W/W A DI Water/Aqua 30 A Dow Corning Dow CaprylylMethicone (and) PEG-12 15.00 EL-7040 Corning/Nexeo Dimethicone/PPG-20Solutions Crosspolymer Slowly disperse into water with propeller mixinguntil a homogeneous gel is obtained B USP Glycerin USP Glycerin 10.00 B3D3P Moisture RF Proprietary Blend*RF 3D3P 10.00 Essence MoistureEssence Ingredient Deck B SD Alcohol 40B Alcohol Denatured 10.00 B DIWater/Aqua 24.50 B Botanistat PF64 Botanigenics Phenoxyethanol (and)capryl 0.50 glycol (and) ethylhexylglycerin (and) hexylene glycol Startmixing liquids with propeller, and slowly disperse into gel phase A.

Example 6—Exemplary Interpenetrating Polymer Network MoisturizingComposition for Use as an Eye Cream

The interpenetrating polymer network moisturizing compositions describedherein (i.e. 3D3P Moisture Essence) can be formulated for use in an eyecream, Table 6.

TABLE 6 3D3P Moisture Essence as an eye cream formulation Phase Tradename Supplier INCI % W/W A 3D3P Moisture RF Proprietary Blend*RF 3D3P15.00 Essence Moisture Essence Ingredient Deck A Dow Corning DowCaprylyl Methicone (and) PEG-12 20.00 EL-7040 Corning/NexeoDimethicone/PPG-20 Crosspolymer Solutions Slowly disperse 3D3P Blendinto DC EL-7040 with propeller mixing until a homogeneous gel isobtained. B DI Water/Aqua 61.20 B SD Alcohol 40B Alcohol Denatured 2.00Botanistat PF64 Botanigenics Phenoxyethanol (and) capryl glycol 0.80(and) ethylhexylglycerin (and) hexylene glycol B Sepiplus 265 SeppicPolyacrylate-13 (and) Polyisobutene 1.00 (and) Polysorbate 20 Startmixing liquids with propeller, and slowly disperse into gel phase A.

Example 7-Exemplary Interpenetrating Polymer Network MoisturizingComposition for Use as an Eye Cream

The interpenetrating polymer network moisturizing compositions describedherein (i.e. 3D3P Moisture Essence) can be formulated for use in an eyecream, Table 7.

TABLE 7 3D3P Eye Cream (30% 3D3P Peach) To Add Trade Name Supplier INCIComponents Phase % w/w (g) 3D3P Moisture Rodan and (formulationdescribed A 30.00 360.00 Essence Fields above) Proprietary Dow CorningDow Corning Caprylyl Methicone 16.00 240.00 EL-7040 PEG-12Dimethicone/PPG- 4.00 20 Crosspolymer Gransil SiW-050 Grant Isododecane0.48 12.00 IS Industries Water 0.21 Dimethicone 0.11 Polysilicone-110.10 Butylene Glycol 0.04 Dimethylacrylamide/Acrylic 0.03Acid/Polystyrene Ethyl Methacrylate Copolymer Coco-Caprylate/Caprate0.025 Caprylyl Glycol 0.001 Phenoxyethanol 0.001 Hexylene Glycol 0.001Decyl Glucoside 0.002 Deionized Water Lab Supply Water B 34.75 417.00Symsave H Symrise Hydroxyacetophenone 0.50 6.00 Dow Corning PF- DowCorning Dimethicone/Vinyl 0.4238 9.00 9510 Elastomer DimethiconeCrosspolymer Water 0.30 C12-14 Pareth-12 0.0188 Phenoxyethanol 0.0056Chlorophenesin 0.0019 Chlorellagen DP Barnet Water 0.975 12.00 ProductsChlorella vulgaris extract 0.025 Corp. CurePassion Ichimaru Water 1.3824.00 Pharcos Butylene Glycol 0.60 Passiflora Edulis Fruit 0.02 ExtractSepiplus 265 Seppic, Inc. Acrylamide/Ammonium C 0.96 19.20 AcrylateCopolymer Polyisobutene 0.448 Polysorbate 20 0.08 Water 0.048 SorbitanIsostearate 0.064 Dow Corning Dow Corning Dimethicone 3.1875 45.00 9576Smooth Dimethicone/Vinyl 0.1313 Away Dimethicone CrosspolymerDimethicone Crosspolymer 0.2813 Beeswax 0.1313 Silica 0.0094 SilicaSilylate 0.0094 ICP Dragon Fruit Devreaux Hylocereus Undatus Fruit 0.9912.00 Extract Specialties Extract Phenoxyethanol 0.008 SodiumMetabisulfite 0.002 Caffeine Ampak Co., Inc. Caffeine 1.00 12.00 SD 40BAlcohol Lab Supply SD 40B Alcohol 2.00 24.00 Sangelose 60L Ikedia Corp.Hydroxypropyl D 0.25 3.00 of America Methylcellulose Stearoxy EtherTimiron Synwhite EMD Fluorphlogopite 0.1152 1.92 40 Performance TitaniumDioxide 0.0432 Materials Tin Oxide 0.0016 FAS70USI White DD ChemcoTitanium Dioxide 0.0891 1.56 Cyclopentasiloxane 0.0325 PEG/PPG 18/180.0065 Dimethicone Triethoxycaprylylsilane 0.002 FAS50EYSI DD ChemcoIron Oxides (CI 77492) 0.049 1.20 Yellow Cyclopentasiloxane 0.0338PEG/PPG 18/18 0.0163 Dimethicone Triethoxycaprylylsilane 0.001 FAS55ERSIRed DD Chemco Iron Oxides (Cl 77491) 0.0049 0.12 Cyclopentasiloxane0.0034 PEG/PPG 18/18 0.0016 Dimethicone Triethoxycaprylylsilane 0.0001

Processing Instructions: 1.) Add phase A items to main vessel. Mixvigorously until a gel is formed. 2.) Premix phase B items. Heat to 40°C. and mix until uniform. 3.) Slowly add phase B to phase A withmoderate mixing. Mix until smooth and uniform. 4.) Add phase C items oneat a time, mixing between additions. Mix until smooth. 5.) Add phase Ditems to match color standard (Pantone 155C). Homogenize until smooth.

Example 8—Exemplary Interpenetrating Polymer Network MoisturizingComposition for Use as an Eye Serum

The interpenetrating polymer network moisturizing compositions describedherein (i.e. 3D3P Moisture Essence) can be formulated for use in an eyeserum, Table 8.

TABLE 8 3D3P Moisture Essence in an eye serum formulation Phase Tradename Supplier INCI % W/W A 3D3P Moisture RF Proprietary Blend*RF 3D3PMoisture 38.5 Essence Essence Ingredient Deck A Dow Corning Dow CaprylylMethicone (and) PEG-12 53.50 EL-7040 Corning/Nexeo Dimethicone/PPG-20Crosspolymer Solutions Slowly disperse 3D3P Blend into DC EL-7040 withpropeller mixing until a homogeneous gel is obtained. B ACQUACELL BarnetWater & Glycerin & Citrullus vulgaris 4.00 (Watermelon) Fruit Extract &Pyrus malus (Apple) Fruit Extract & Lens Esculenta (Lentil) FruitExtract & Sodium PCA & Sodium Lactate B SymGlucan Symrise Aqua,Glycerin, Beta-Glucan 4.00 Start mixing liquids with propeller, andslowly disperse into gel phase A.

Example 9: Exemplary Interpenetrating Polymer Network Composition forUse as a Teen Acne Wash

The interpenetrating polymer network moisturizing compositions describedherein (i.e. 3D3P Moisture Essence) can be formulated for use in a teenacne wash, Table 9.

TABLE 9 Teen Acne Wash To Add Trade Name Supplier INCI Components Phase% w/w (g) 3D3P Moisture Rodan and (formulation described A 15.00 120.00Essence Fields above) Proprietary Diglycerin S Rossow Diglycerin 3.0024.00 Barsolve NS-100 Barnet Polyglyceryl-10 3.00 24.00 Products Corp.Laurate GT-730 Adeka Corp. PEG-240/HDI 0.07 8.00 Copolymer Bis-Decyltetradeceth-20 Ether Butylene Glycol 0.12 Water 0.80 PotassiumLaurate 0.0075 Tocpherol 0.0025 Iselux Ultra Mild Chem Tech Water 6.5480.00 Sodium Lauroyl 1.20 Methyl Isethionate Cocamidopropyl 0.90 BetaineSodium Methyl Oleoyl 0.70 Taurate Lauryl Glucoside 0.30 Coco-Glucoside0.30 Sodium Benzoate 0.06 Citric Acid Spectrum Citric Acid 1.00 8.00Granular Chemical Mfg. Corp. GlycoFilm 1.5P Solabia Water 2.919 24.00Biosaccharide Gum 4 0.036 Phenoxyethanol 0.045 Lipacide C8G Seppic, Inc.Capryloyl Glycine 0.50 4.00 Stearic Acid AE Chemie, Inc. Stearic Acid3.00 24.00 Amilite GCS-11 Ajinomoto Sodium Cocoyl B 20.00 160.00Glycinate Glycerin Jeen Chemical, Glycerin 7.00 56.00 Inc.AmisafeLL-DS-22 Ajinomoto Disodium Sebacoyl 0.05 4.00Bis-Lauramidolysine Water 0.45 Deionized Water Lab Supply Water 19.30154.40 Symsave H Symrise Hydroxyacetophenone 0.50 4.00 Curoxyl 42Vantage Benzoyl Peroxide C 5.00 100.00 Water 7.50 Sepimat HBV Seppic,Inc. Methyl Methacrylate 0.50 4.00 Crosspolymer Menthol Ampak, Co.Menthol 0.20 1.60

Mixing Instructions: 1.) Mix phase A and heat to 65° C. 2.) At 65° C.,add Phase B ingredients, one at a time, mixing between additions.Continue mixing until smooth and uniform. 3.) Begin cooling to 30° C.with slow mixing. At 30° C., add phase C ingredients one at a time,mixing between additions. Mix until smooth and uniform.

Example 10—Dynamic Vapour Sorption (DVS) Testing

One sample of glycerin (1505-56) and three polysaccharide in glycerinsamples (1505-57, 1505-58, and 1505-59) were tested using the dynamicvapor sorption (DVS) analyses. The formulation for each is provided inTable 10.

TABLE 10 Test sample formulations 1505-59 (AKA 1505-21 1505- 1505- 1505-or 3D3P 56 57 58 Moisture % % % Essence) Trade name Supplier INCI W/WW/W W/W % W/W DI Water/Aqua 0 0 49.83 49.83 Kelcogel Univar/Kelco GellanGum 0 0 0.03 0.03 CG-HA CP Kelcogel Univar/Kelco Gellan Gum 0 0 0.080.08 CG-LA CP USP USP Glycerin 100.00 99.00 27.00 27.00 GlycerinBotanimoist Botanigenics Pyrus Malus (Apple) 0 0 0 1.00 AMS FruitExtract (and) Glycerin Hydrolite 5 Symrise Pentylene Glycol 0 0 0 3.00Gransil VX- Grant Bis-PEG-12 0 0 0 3.00 419 Industries DimethiconeBotanistat Botanigenics Phenoxyethanol (and) 0 0 0 0.70 PF64 caprylglycol (and) ethylhexylglycerin (and) hexylene glycol DistinctiveResources of Sodium Hyaluronate 0 1.30 0.12 0.12 Bio Sodium NatureHyaluronate (#10094) Polysurf Ashland Cetyl 0 0 0.30 0.30 67CShydroxyethylcellulose DI Water/Aqua 0 0 10.00 10.00 OriStar ADS OriStarAdenosine 0 0 0 0.04 Magnolidone Solabia Magnesium PCA 0 0 0.30 0.30Calcidone Solabia Calcium PCA 0 0 0.30 0.30 OriStar Sodium benzoate 00.10 0 0.10 Earth ESP Sea Salt Fine 0 0 0 0.10 Supplied Products 90%lactic 0 0 0 0.10 acid (dilute if needed) Distinctive ® Resources ofGlycerin (and) 0 0 0 3.00 Bio-Signal Nature Phosphatidylglycerol LipidRF-II (DC4038) Skinmimics ® Evonik Ceteareth-25; Glycerin; 0 0 0 1.00Cetyl Alcohol; Behenic Acid; Cholesterol; Ceramide NP; Ceramide NS;Ceramide EOS; Ceramide EOP; Ceramide AP; Caprooyl Phytosphingosine;Caprooyl Sphingosine 100.00

Results and Discussion: It was determined that glycerin lot RF 1505-56and polysaccharide in glycerin lots RF 1505-58 and RF 1505-59 were ableto be directly introduced into the titration vessel given theirsolubility in the methanol-based solvent. Polysaccharide in glycerin lotRF 1505-57 was not soluble in the methanol-based solvent or other commonsolvent combinations and had to be analyzed using the oven.

The samples be dried in an oven at 105° C. for four hours prior toanalysis of the samples. The water content values for the individualreplicates for each of the samples as well as the average water contentare reported in Table 11.

TABLE 11 Water Content results Water Average Water Replicate AmountContent Content Sample No. Method No. (g) (%) (%) 1505-56 Wet 1 0.37911.51 1.49 2 0.2950 1.48 3 0.4189 1.49 1505-57 Oven 0.5750 1.80 1.801505-58 Wet 1 0.0371 45.11 45.37 2 0.0401 45.25 3 0.0544 45.75 1505-59Wet 1 0.0660 31.82 31.75 2 0.0567 31.82 3 0.0407 31.61

Dynamic vapour sorption (DVS) is a technique that measures the uptakeand loss of moisture of a material by passing a carrier gas of knownhumidity over a sample contained in a weighing mechanism. The weightversus time curves for the DVS data from the four samples are presentedin FIGS. 1, 3, 5, and 7 while the percent weight change versus percentrelative humidity (RH) curves are presented in FIGS. 2, 4, 6, and 8,respectively. The DVS results are summarized in Table 12.

TABLE 12 Summary of DVS Results Samples Sorption/Desorption* 1505-560.07% loss upon drying at 5% RH 36.93% gain from 5 to 95% RH 7.42% gainfrom 95% to 75% RH 33.92% loss from 75 to 5% RH 1505-57 0.15% loss upondrying at 5% RH 53.82% gain from 5 to 95% RH 7.51% gain from 95% to 75%RH 52.12% loss from 75 to 5% RH 1505-58 22.12% loss upon drying at 5% RH11.33% loss from 5 to 35% RH 28.27% gain from 35% to 95% RH 3.66% gainfrom 95 to 85% RH 36.41% loss from 85 to 5% RH 1505-59 18.11% loss upondrying at 5% RH 3.11% gain from 5 to 15% RH 106.56% gain from 15% to 95%RH 11.95% gain from 95 to 85% RH 107.92% loss from 85 to 5% RH *RH =relative humidity; All percent weight change values are calculated withrespect to the initial starting weight.

Conclusions: The KF results showed that the glycerin lot RF 1505-56 andpolysaccharide in glycerin lot RF 1505-57 had similar water contentsbelow 2% after drying. Polysaccharide in glycerin lots RF 1505-58 and RF1505-59 had significantly higher water contents than the other twosamples with lot RF 1505-58 showing the highest water content afterdrying.

Example 11—A Single Center, Double-Blind Clinical Trial Assessing theEfficacy of Hydrating Essences when Used by Women with PhotodamagedFacial Skin

Photodamaged/aged facial skin is characterized by a dull appearance andthe presence of fine lines, wrinkles, and mottled pigmentation, amongother changes that contribute to visual signs of aging. Fine lines andwrinkles arise due to the breakdown of collagen, while decreases in theamount of water held in the epidermis result in the accentuation of finelines as well as visible and tactile skin roughness.

This single-center, double-blind clinical trial was conducted over thecourse of 8 days to assess the efficacy of the Sponsor's hydratingessence when used by women with mild to moderate dry skin, global finelines, and skin dullness on the face. A total of 39 subjects completedstudy participation in 1 of the following treatment cells: Cell 1 (14subjects): Formulation 1505-21 (Table 10), Cell 2 (13 subjects):Formulation 1505-42B (Table 13), Cell 3 (12 subjects): Formulationbenchmark/Amore Pacific.

TABLE 13 Formulation 1505-42B INCI CAS # % w/w DI Water/Aqua 7732-18-554.50% Caprylyl Methicone 17955-88-3 12.50% PEG-12 Dimethicone/PPG-1310362-62-9 20 Crosspolymer Alcohol Denatured 64-17-5 10.00%Proprietary Blend*RF 3D3P Moisture Essence Ingredient 10.00% Deck (seeTable 2 and 3) Glycerin 56-81-5 8.00% Isododecane 13475-82-6 1.00%Dimethicone 9006-65-9, 63148-62-9 Polysilicone-11 63394-02-5 ButyleneGlycol 107-88-0 Dimethylacrylamide/Acrylic 547763-79-1 Acid/PolystyreneEthyl Methacrylate Copolymer Coco-Caprylate/Caprate 95912-86-0 DecylGlucoside 58846-77-8 Hydroxyethyl 111286-86-3 2.10% Acrylate/SodiumAcryloyldimethyl Taurate Copolymer Isohexadecane 63793-60-2 Polysorbate60 9005-67-8 Pentylene Glycol 5343-92-0 1.50% Phenoxyethanol 122-99-60.40% Capryl Glycol 1117-86-8 Ethylhexylglycerin 70445-33-9 HexyleneGlycol 107-41-5

During the course of the study, subjects applied the assigned testmaterial to the entire face every evening after cleansing and toning, asdirected. Subjects also performed an in-clinic application on day 1 andday 8. Clinical evaluations were conducted at visit 1 (baseline[pre-application] and 30 minutes post-application), visit 2 (8 hourspost-application), and visit 3 (day 8: pre-application and 30 minutespost-application). See Table 14 for Study outline.

TABLE 14 Study Outline Time points Day 1 Day 1 Day 8 Day 8 Day 1 30 mins8 hrs Days (pre- 30 mins Procedures (BL) PA PA 2-7 application) PAClinical X In-Clinic X X X In-Clinic X Grading Product Product (Radiance& Application Application Fine Lines) Corneometer X X X X X MeasurementsSKICON X X X X X Measurements Tewameter X X Measurements Cutometer X X XX X Measurements Self- X X X X X Evaluation w/ VAS scale Self- X X X X XAssessment Questionnaires In-Home X Product Application Daily Diaries XBL = baseline, PA = post-application

Subjects participated in the following procedures at each of the timepoints (unless otherwise indicated):

1) Clinical Grading of Efficacy Parameters: Subjects were clinicallygraded globally on the face for radiance, fine lines, and overalldryness.

2) Corneometer Measurements: Triplicate Corneometer CM 825(Courage+Khazaka, Germany) measurements were taken on the center of eachsubject's cheek to measure the moisture content in the stratum corneum.Measurement is based on the capacitance measurement of a dielectricmedium.

3) SKICON Measurements: Triplicate SKICON-200EX (I.B.S. Co., Ltd.,Japan) measurements were taken on the center of each subject's cheek tomeasure test material effects on the moisture content of the stratumcorneum. Measures conductance.

4) Tewameter Measurements: At pre-application on day 1 and day 8, asingle Tewameter TM300 (Courage+Khazaka, Germany) measurement was takenon the center of each subject's cheek to assess passive water transportthrough the stratum corneum (transepidermal water loss [TEWL]). Measuresthe density gradient of water evaporation from the skin indirectly by 2pairs of sensors (temperature and relative humidity).

5) Cutometer Measurements: A single Cutometer MPA 580 (Courage+Khazaka,Germany) measurement was taken on the lower edge of the orbit (directlybeneath the center of the eye) of each subject to measure theviscoelastic properties of the skin. Measures elasticity.

6) Subject Rating of Skin Attributes: Subjects used a mirror to evaluateand rate specific facial skin attributes.

7) Self-Assessment Questionnaire: Subjects completed a Sponsor-providedself-assessment questionnaire regarding test material efficacy andattributes at each post-baseline time point.

Corneometer and Cutometer measurements were taken on 1 side of the face(right or left) and SKICON and Tewameter measurements were taken on theopposite side of the face, in accordance with a predeterminedrandomization.

Overall Conclusions: Overall results from this single-center,double-blind, clinical trial indicate that the Sponsor's test materials[Cell 1: Formulation 1505-21, Cell 2: Formulation 1505-42B, and Cell 3:Formulation benchmark/Amore Pacific] were effective in improving facialskin condition and moisturization over the course of 8 days of use bywomen with mild to moderate facial dry skin, fine lines, and skindullness under the conditions of this test.

For clinical grading of efficacy parameters, all 3 cells showed astatistically significant increase (improvement) in scores for radianceand fine lines at each post-baseline time point (30 minutespost-application on day 1, 8 hours post-application on day 1,pre-application on day 8, and 30 minutes post-application on day 8) andfor overall dryness at pre- and post-application on day 8 when comparedwith baseline (day 1 pre-application) scores.

All 3 cells produced a statistically significant improvement in themoisturization of the stratum corneum, with a statistically significantincrease (improvement) in values for Corneometer and SKICON measurementsat each post-baseline time point when compared with baseline values. ForTewameter measurements, there was a statistically significant decrease(improvement) for Cell 3 at day 8 pre-application and no statisticallysignificant change from baseline for Cell 1 and Cell 2.

Analysis of the Cutometer measurements showed the followingstatistically significant differences when compared with baseline (day 1pre-application) values: decrease in extensibility at 8 hourspost-application on day 1 for Cell 3; increase in resiliency for Cell 2at 8 hours post-application on day 1 and 30 minutes post-application onday 8; and increase in pure elasticity for Cell 1 and Cell 2 at 30minutes post-application on day 8. Results of the Cutometer measurementsindicate that Cell 1: Formulation 1505-21 and Cell 2: Formulation1505-42B for helping improve skin elasticity and Cell 3: Formulationbenchmark/Amore Pacific for helping improve skin firmness.

Analysis of the subject rating of skin attributes showed that subjectsin all 3 cells indicated a statistically significant improvement intheir perceptions of the following attributes at each post-baseline timepoint when compared with baseline response values: moisturization (feeland appearance), fine lines [excluding Cell 3 at 30 minutespost-application on day 1], radiance, suppleness, softness, smoothness,bouncy skin, dryness, overall appearance, and overall comfort. Analysisof the self-assessment questionnaires completed by subjects atpost-baseline time points indicated that a statistically significantproportion of subjects in all 3 treatment cells selected favorableresponses to almost all of the inquiries (regarding applicationexperience, improvements in skin appearance and feel, comparison to pastmoisturizers used, etc.) at each asked time point.

Comparisons among the treatment cells indicated that all 3 testmaterials were generally equally effective for improving facial skincondition, providing moisturization, and subject perceptions (throughrating of skin attributes and self-assessment questionnaires), althougha few statistically significant differences were noted between treatmentcells for efficacy parameter grading, Corneometer, and SKICON.

Procedures and Methods: During the course of the study, applicableclinic rooms were maintained at a temperature of 68° F. to 75° F. andthe relative humidity ranged from 35% to 65%. After the acclimationperiod, candidate subjects were evaluated for the Fitzpatrick SkinClassification and the Presence of Facial Dryness/Aging.

The Fitzpatrick Skin Classification is based on the skin's unprotectedresponse to the first 30 to 45 minutes of sun exposure after a winterseason without sun exposure. Types I-VI qualified (approximately 80% ofsubjects having types I-IV and the remaining subjects having typesV-VI). The categories of skin types are described in Table 15.

TABLE 15 Fitzpatrick Skin Classification Type Physical CharacteristicsSkin Reaction to UV I White; very fair; red or blonde hair; Always burnseasily; blue eyes; freckles never tans II White; fair; red or blondehair; blue, Always burns easily; hazel, or green eyes tans minimally IIICream white; fair with any eye or hair Burns moderately; color; verycommon tans gradually IV Brown; typical Mediterranean white skin Burnsminimally; always tans well V Dark Brown; mid-eastern skin types, Rarelyburns; tans black hair, olive skin profusely VI Black; black hair, blackeyes, black skin Never burns; deeply pigmented

Presence of Facial Dryness/Aging: Clinically determined mild to moderate(score of 3-6 according to modified Griffiths' scale2 where 0=none and9=severe) facial dryness, global facial fine lines, and facial skindullness.

Evaluation Procedure:

1) Clinical Grading of Efficacy Parameters: Subjects were clinicallygraded for the following efficacy parameters globally on the face usinga modified Griffiths' 10-point scale according to the followingnumerical definitions (with half-point scores assigned as necessary toaccurately describe the skin condition): 0=none (best possiblecondition), 1 to 3=mild, 4 to 6=moderate, 7 to 9=severe (worst possiblecondition). The following parameters were graded according to the listedscale anchors: Radiance 0=Radiant, luminous appearance and 9=Dull/matteand or/sallow appearance, Fine lines 0=none and, 9=Numerous, deep finelines, Overall dryness 0=Not dry, plump, smooth, soft feeling and9=Severe dryness, dull, rough feeling, flaking/scaling.

2) Corneometer Measurements: Triplicate Corneometer CM 825(Courage+Khazaka, Germany) measurements were taken on the center of eachsubject's cheek (at the intersection of lines extending down from theouter corner of the eye and horizontally across the bottom of the nose)to measure product hydration effects on the skin surface. TheCorneometer measures moisture content in the stratum corneum by anelectrical capacitance method. The measurement has no units, but isproportional to the dielectric constant of the surface layers of theskin, and increases as the skin becomes more hydrated. The readings aredirectly related to the skin's electrical capacitance (picofarads).

3) SKICON Measurements: Triplicate SKICON-200EX (I.B.S. Co., Ltd.,Japan) measurements were taken on the center of each subject's cheek (atthe intersection of lines extending down from the outer corner of theeye and horizontally across the bottom of the nose) to measure testmaterial effects on the moisture content of the stratum corneum. SKICONmeasures test material effects on the moisture content in the stratumcorneum using high frequency conductance methodology. Data is collectedin micro Siemens (0), and measurements increase with skin hydration.

4) Tewameter Measurements: A single Tewameter TM300 (Courage+Khazaka,Germany) measurement was taken on the center of each subject's cheek (atthe intersection of lines extending down from the outer corner of theeye and horizontally across the bottom of the nose) to assess passivewater transport through the stratum corneum (transepidermal water loss[TEWL]). The measurement of this water evaporation is based on thediffusion principle in an open chamber, and the density gradient ismeasured indirectly by 2 pairs of sensors located inside the hollowcylinder probe. Data are analyzed by a microprocessor and reported ing/m2/h. A decrease in TEWL values reflects an improvement in the barrierproperties of the skin.

5) Cutometer Measurements: A single Cutometer MPA 580 (Courage+Khazaka,Germany) measurement was taken on the lower edge of the orbit (directlybeneath the center of the eye) of each subject to measure theviscoelastic properties of the skin. Negative pressure of 300 mbar wasapplied and released through an 8-mm probe (standard settings). Themeasurement lasts for 30 seconds, during which are 2 repeated cycles ofa 5-second on (vacuum) time and a 10-second off (skin release) time. Themovement of the skin into and out of the probe was recorded during theapplication and release of suction. The amount of extensibility,resiliency, pure elasticity and biological elasticity were recorded.

6) Subject Rating of Skin Attributes: Subjects used a mirror to evaluateand rate specific facial skin attributes according to a 10-point scalewhere 1=worst condition and 10=best condition.

Subjects were instructed to follow their normal morning skin careroutine and to apply the assigned test material to the entire face everyevening after cleansing and toning. Subjects were distributed apre-weighed unit of the cell-specific test material and written/verbalusage instructions: Cell 1 (Formulation 1505-21)—Before each use, twistopen the base of the cap of the Essence counterclockwise. Once twistedoff, push down on the button on top of the cap to expel the entirecontents of the dropper into the palm of your hand. Rub hands togetherand with both hands smooth product evenly over your entire face andallow to dry. Use 1 pump per application. Follow with the rest of yournighttime skincare regimen. Do not apply essence on eye lids. Avoidgetting into eyes. Cell 2 (Formulation 1505-42B)—Apply 1-2 pumps ofproduct evenly to your entire face. Follow with the rest of yournighttime skincare regimen. Cell 3 (Formulation benchmark)/AmorePacific)—Apply 1-2 pumps of product evenly to your entire face. Followwith the rest of your nighttime skincare regimen.

Subjects performed the first application of the assigned test materialin the clinic, under the supervision of clinic personnel. Approximately30 minutes after application, clinical grading of efficacy parameters,bioinstrumentation measurements (Corneometer, SKICON, and Cutometer),and subject rating of skin attribute procedures were repeated asdescribed for baseline. Additionally, subjects completed aSponsor-provided self-assessment questionnaire regarding test materialefficacy and attributes.

Subjects were provided with a calendar of study visits and a daily diaryto record product application times and comments. Subjects wereinstructed not to apply any products to the face or engage in anyactivity which may remove the test material from the face (cleansing,exercise/sweat, etc.) until after completion of visit 2 (day 1/hour 8).

Subjects returned to the clinic for visit 2 (day 1), approximately 8hours after test material application. Clinic personnel recordedconcomitant medications, questioned subjects regarding changes in theirhealth, and AEs were recorded if applicable.

Subjects acclimated to ambient temperature and humidity conditions forat least 15 minutes and then participated in the following evaluationsas described for baseline: clinical grading of efficacy parameters,bioinstrumentation measurements (Corneometer, SKICON, and Cutometer),and subject rating of skin attributes. Subjects also completed aSponsor-provided self-assessment questionnaire.

Subjects returned to the clinic for visit 3 (day 8) and participated inthe following procedures: Clinic personnel recorded concomitantmedications and questioned subjects regarding changes in their health.AEs were recorded if applicable. Daily diaries were collected, reviewedfor compliance, and retained by the clinic. Subjects acclimated for atleast 15 minutes and then participated in the following evaluationprocedures as described for baseline: Clinical grading of efficacyparameters was performed. Bioinstrumentation measurements (Corneometer,SKICON, Tewameter, and Cutometer) were performed. Subjects rated skinattributes and completed a Sponsor-provided self-assessmentquestionnaire. After completion of day 8 baseline (pre-application)procedures, subjects performed an in-clinic application of the testmaterial. Test material units were collected, visually inspected andweighed for compliance, and retained by the clinic. Approximately 30minutes after test material application, clinical grading of efficacyparameters, bioinstrumentation measurements (Corneometer, SKICON, andCutometer), subject rating of skin attributes, and subject completion ofSponsor-provided self-assessment questionnaire were repeated.

Results

Efficacy Parameter Clinical Grading: Use of the Sponsor's test materials[Cell 1: Formulation 1505-21, Cell 2: Formulation 1505-42B, and Cell 3:Formulation benchmark/Amore Pacific] produced a statisticallysignificant decrease (improvement) in clinical grading scores forradiance and fine lines at each post-baseline time point (30 minutespost-application on day 1, 8 hours post-application on day 1,pre-application on day 8, and 30 minutes post-application on day 8) whencompared with baseline (day 1 pre-application) scores, see FIG. 9A(radiance) and 9B (fine lines). For grading of overall dryness, therewas a statistically significant decrease (improvement) in scores forCell 3: Formulation benchmark/Amore Pacific at all post-baseline timepoints and for Cell 1: Formulation 1505-21 and Cell 2: Formulation1505-42B at pre-application and 30 minutes post-application on day 8when compared with baseline scores. [Note that due to the timing of theprotocol amendment implementation, only 1 subject in cells 1 and 2 weregraded at the 30 minute and 8 hour post-application time points on day1, which is why there are no statistically significant changes frombaseline for these cells and time points.] Comparisons among thetreatment cells, based on the mean change from baseline for efficacyparameters, indicated that Cell 3 produced a statistically significantgreater improvement in radiance and fine lines at 30 minutespost-application on day 1 compared to Cell 1 and Cell 2, and in overalldryness at 30 minutes post-application on day 8 compared to Cell 1.

Corneometer Measurements: Use of the Sponsor's test materials [Cell 1:Formulation 1505-21, Cell 2: Formulation 1505-42B, and Cell 3:Formulation benchmark/Amore Pacific] produced a statisticallysignificant increase (improvement) in Corneometer measurement values ateach post-baseline time point (30 minutes post-application on day 1, 8hours post-application on day 1, pre-application on day 8, and 30minutes post-application on day 8) when compared with baseline (day 1pre-application) values. Comparisons among the treatment cells, based onthe mean change from baseline for Corneometer measurements, indicated nostatistically significant differences among the treatment cells at anytime points. See FIG. 10. FIGS. 11A, 11B, and 11C represent 3 subjects,each demonstrating that the moisture level of the individuals skinadjusted to an individualized level.

SKICON Measurements: Use of the Sponsor's test materials [Cell 1:Formulation 1505-21, Cell 2: Formulation 1505-42B, and Cell 3:Formulation benchmark/Amore Pacific] produced a statisticallysignificant increase (improvement) in SKICON measurement values at eachpost-baseline time point (30 minutes post-application on day 1, 8 hourspost-application on day 1, pre-application on day 8, and 30 minutespost-application on day 8) when compared with baseline (day 1pre-application) values, see FIG. 12. Comparisons among the treatmentcells, based on the mean change from baseline for SKICON measurements,indicated that Cell 1 produced a statistically significant greaterimprovement at 30 minutes and 8 hours post-application on day 1 comparedto Cell 2 and Cell 3, and at 30 minutes post-application on day 8compared to Cell 3.

Tewameter Measurements: Use of the Sponsor's test material for Cell 3:Formulation benchmark/Amore Pacific produced a statistically significantdecrease (improvement) in Tewameter measurement values at day 8pre-application when compared with baseline (day 1 pre-application)values. There were no statistically significant changes from baseline inTEWL values for Cell 1: Formulation 1505-21 and Cell 2: Formulation1505-42B at day 8 pre-application. Comparisons among the treatmentcells, based on the mean change from baseline for Tewametermeasurements, indicated no statistically significant differences amongthe treatment cells at day 8 pre-application.

Cutometer Measurements: Analysis of the Cutometer measurements for eachtreatment cell showed the following statistically significantdifferences (improvements) when compared with baseline (day 1pre-application) values: Extensibility (R0): decrease for Cell 3 at 8hours post-application on day 1, Resiliency (R2): increase for Cell 2 at8 hours post-application on day 1 and 30 minutes post-application on day8, Pure Elasticity (R5), see FIG. 13: increase for Cell 1 and Cell 2 at30 minutes post-application on day 8. There were no statisticallysignificant changes from baseline for biological elasticity (R7) at anypost-baseline time point for any of the treatment cells. Comparisonsamong the treatment cells, based on the mean change from baseline forCutometer measurements, indicated no statistically significantdifferences among the treatment cells at any post-baseline time point.

Subject Rating of Skin Attributes: Use of the Sponsor's test materials[Cell 1: Formulation 1505-21, Cell 2: Formulation 1505-42B, and Cell 3:R Formulation benchmark/Amore Pacific] produced a statisticallysignificant increase (improvement) in subject response values for thefollowing attributes at each post-baseline time point (30 minutespost-application on day 1, 8 hours post-application on day 1,pre-application on day 8, and 30 minutes post-application on day 8) whencompared with baseline (day 1 pre-application) values (unless otherwiseindicated): Moisturization (skin feel), Moisturization (appearance),Fine lines (appearance)—excluding Cell 3 at 30 minutes post-applicationon day 1, Radiance (appearance, see FIG. 14A), Suppleness (elasticity,snap back, firmness, see FIG. 14B), Softness (to touch), Smoothness (totouch), Bouncy skin (to touch, see FIG. 14C), Dryness (appearance),Overall appearance, Overall comfort (feel). There was also astatistically significant improvement in response values for “Tightness”for Cell 2 at all time points and for Cell 3 at 8 hours post-applicationon day 1 and 30 minutes post-application on day 8 when compared withbaseline values. Comparisons among the treatment cells, based on themean change from baseline for skin attribute rating parameters,indicated no statistically significant differences among the treatmentcells at any post-baseline time point.

Self-Assessment Questionnaire: Results of the analyses of theself-assessment questionnaires completed by subjects at eachpost-baseline time point showed that a statistically significantproportion of subjects in all 3 cells selected favorable responsescompared to unfavorable responses at the indicated time points (unlessotherwise indicated). Comparisons among the treatment cells, based onthe proportion of favorable responses, showed that a greater proportionof subjects in Cell 3 selected favorable responses compared to Cell 2for the question “Did you notice a difference in how youthful your skinlooks after using the product?” at 30 minutes post-application on day 1.

Discussion and Conclusions

Overall results from this single-center, double-blind, clinical trialindicate that the Sponsor's test materials [Cell 1: Formulation 1505-21,Cell 2: Formulation 1505-42B, and Cell 3: Formulation benchmark/AmorePacific] were effective in improving facial skin condition andmoisturization over the course of 8 days of use by women with mild tomoderate facial dry skin, fine lines, and skin dullness under theconditions of this test. FIG. 15 shows the photograph of dry skin beforeand 15 minutes after the application of Formulation 1505-21.

For clinical grading of efficacy parameters, all 3 cells showed astatistically significant increase (improvement) in scores for radianceand fine lines at each post-baseline time point (30 minutespost-application on day 1, 8 hours post-application on day 1,pre-application on day 8, and 30 minutes post-application on day 8) andfor overall dryness at pre- and post-application on day 8 when comparedwith baseline (day 1 pre-application) scores.

All 3 cells produced a statistically significant improvement in themoisturization of the stratum corneum, with a statistically significantincrease (improvement) in values for Corneometer and SKICON measurementsat each post-baseline time point when compared with baseline values. ForTewameter measurements, there was a statistically significant decrease(improvement) for Cell 3 at day 8 pre-application and no statisticallysignificant change from baseline for Cell 1 and Cell 2.

Analysis of the Cutometer measurements showed the followingstatistically significant differences when compared with baseline (day 1pre-application) values: decrease in extensibility at 8 hourspost-application on day 1 for Cell 3; increase in resiliency for Cell 2at 8 hours post-application on day 1 and 30 minutes post-application onday 8; and increase in pure elasticity for Cell 1 and Cell 2 at 30minutes post-application on day 8. Results of the Cutometer measurementsindicate that Cell 1: Formulation 1505-21 and Cell 2: Formulation1505-42B for helping improve skin elasticity and Cell 3: Formulationbenchmark/Amore Pacific for helping improve skin firmness.

Analysis of the subject rating of skin attributes showed that subjectsin all 3 cells indicated a statistically significant improvement intheir perceptions of the following attributes at each post-baseline timepoint when compared with baseline response values: moisturization (feeland appearance), fine lines (excluding Cell 3 at 30 minutespost-application on day 1), radiance, suppleness, softness, smoothness,bouncy skin, dryness, overall appearance, and overall comfort. Analysisof the self-assessment questionnaires completed by subjects atpost-baseline time points indicated that a statistically significantproportion of subjects in all 3 treatment cells selected favorableresponses to almost all of the inquiries (regarding applicationexperience, improvements in skin appearance and feel, comparison to pastmoisturizers used, etc.) at each asked time point.

Comparisons among the treatment cells indicated that all 3 testmaterials were generally equally effective for improving facial skincondition, providing moisturization, and subject perceptions (throughrating of skin attributes and self-assessment questionnaires), althougha few statistically significant differences were noted between treatmentcells for efficacy parameter grading, Corneometer, and SKICON.

Example 12: Treating Xerosis with a Novel Interpenetrating PolymerNetwork

Xerosis, or abnormally dry skin, can stem from a variety of causes fromthe environment to underlying medical conditions and humectants arecommonly used to treat this dry, itchy and flaky skin. Glycerol andhyaluronic acid (HA) are widely used as humectants but often simplydeposit at the surface of the skin being too hydrophilic to interactwith the dry, hydrophobic and compacted stratum corneum. This work setout to improve the delivery of glycerol and HA by designing ahydrophobically-modified interpenetrating polymer network (IPN) forsuperior substantivity, delivery and hydration at the stratum corneum.

A 3D3P (3 dimensional 3 polymer)-IPN (interpenetrating polymer network),chemically depicted in FIG. 16B, was created from gellan gum,hydrophobically-modified cellulose and a linear sodium hyaluronate.Magnesium and calcium ions were added in the form of PCA salts tocross-link the gellan gum forming a gelatinous 3D3P-IPN. Glycerol wasintroduced to attract and bind water and calcium ions, as a salt ofpyroglutamic acid, to support barrier homeostasis. The super-humectant3D3P-IPN composition was examined with both in vitro and in vivotechniques to determine the effectiveness in restoring hydration levelsat the stratum corneum and the capacity to attract and bind watermolecules.

Methods:

Karl Fischer and Dynamic Vapor Sorption (DVS) Analysis: Dynamic vaporsorption (DVS) technique was utilized to study water sorptioncharacteristics of 3D3P-IPN versus glycerol and a mixture of glyceroland sodium hyaluronate, which are commercially common humectantsformulated in moisturizing products. It should be noted that it wasfound that the 3D3P-IPN composition could not be fully dehydrated in adrying oven (105° C.) prior to starting the sorption study. Percentmoisture concentration was analyzed in each sample with a Karl Fishertitration technique. The samples where then exposed to an increasingrelative humidity (RH) over a period of 1200 minutes while measured forweight gain/loss with respect to RH and time. The Karl Fischer analysiswas performed using a Mettler Toledo model V20 volumetric titratorinterfaced with a D0308 drying oven for the drying stage of analysis.The oven set at 260° C. A nitrogen stream set a flow rate of 50mL/minute was used to transfer the moisture from the sample to thetitration vessel.

In vivo Capacitance: A leading commercial moisturizer product controlwas selected with a high concentration of glycerol and a mixture ofother humectants including sodium hyaluronate, hydroxyethyl cellulose,butylene glycol, betaine, beta-glucan, magnesium aspartate, zincgluconate, copper gluconate, and calcium gluconate to compare againstthe 3D3P-IPN delivery scaffold for skin hydration. A corneometercapacitance technique was used to measure the changes in hydration overan eight day period on twelve human subjects ranging in mild to severedry skin conditions.

Results:

The ability of 98% glycerol in 1.3% 3D3P-IPN to absorb moisture wasdetermined by dynamic vapor sorption (DVS) and compared to 98% glycerolalone and 98% glycerol plus 1.3% sodium hyaluronate. Percent moistureconcentration was analyzed in each sample with a Karl Fisher titrationtechnique. The samples where then exposed to an increasing relativehumidity (RH) over a period of 1200 minutes while measured for weightgain/loss with respect to RH and time. The 1.3% 3D3P-IPN plus 30%glycerol in water absorbed significantly more moisture (31.75%) than 98%glycerol (1.40-1.49%) and 98% glycerol plus 1.3% sodium hyaluronate(1.80-1.89%). This DVS data demonstrates that the 3D3P-IPN is capable ofincreasing the hygroscopic properties of glycerol.

When all three samples were equilibrated to 5% RH each lost furthermoisture increasing in loss from glycerol alone to glycerol plus sodiumhyaluronate to glycerol plus 3D3P-IPN (FIG. 17). It was subsequentlyobserved that the 3D3P-IPN composition in glycerol with other humectantswas capable of absorbing a significantly greater amount of water duringthe period when the sample was exposed to a starting relative humidityof 5% which increased over time to 95% (FIG. 17).

A corneometer capacitance technique was used to measure the changes inhydration over an eight-day period on twelve subjects with mild tosevere dry skin with daily use of 30% glycerol 3D3P-IPN. Hydrationincreased from a baseline average (38.31) after one application (60.94)which was maintained throughout the day (56.29). On day 8 beforeapplication, this level was still maintained (59.47) and 30 minutesafter application, this rose to a peak level (75.06). FIG. 18 shows thatboth the commercial hydration product and 3D3P-IPN 30% glycerol producedand increase in skin surface hydration 30 minutes post firstapplication. Of interest is that this moisture is better retained in the3D3P-IPN glycerol subjects at the end of day one, produces a moreelevated moisture level through continued use and results in anincreased cumulative moisture level after 8 days at baseline. It shouldalso be noted the subsequent rise post application producing a differentin relative scores of 55.69 for the commercial product versus 75.06 for3D3P-IPN glycerol.

Conclusion:

An interpenetrating polymer network can be created with gellan gum,modified cellulose and sodium hyaluronate stabilized with calcium andmagnesium (3D3P-IPN). Glycerol and hyaluronic acid can be enhanced inboth hydroscopic properties and skin hydrating performance whenentrapped in a highly substantive IPN. When combined with 30% glycerol3D3P-IPN can attract and retain moisture more effectively than 98%glycerol an 98% glycerol plus hyaluronic acid. 3D3P-IPN 30% glycerol canimprove the moisture level of the skin surface more effectively in theshort term and with continued use than a leading hydrating commercialproduct. The ability for an IPN to attract moisture to the skin andretain it at the skin's surface provides an improved system to support akey dermatological endpoint of generating and maintaining a wellhydrated stratum corneum. This benefit is demonstrated in FIG. 15.

Example 13: Treating Roughness with a Novel Interpenetrating PolymerNetwork

VisioScan Imaging Procedures: VisioScan VC 98 (Courage+Khazakaelectronic GmbH), which is a UVA-light (340-400 nm) video camera withhigh resolution was utilized to study the skin surface directly, and tocapture images of each subject's right cheek. The image captures skinsurface texture, dryness, and pigmentation. The imaging area is 6 mm×8mm at a resolution of 480×640 pixels. VisioScan software was used tocalculate and analyze the images for skin texture/roughness parameters.

Analysis of the VisioScan images for roughness parameters (measurementsR1-R5) showed no statistically significant differences from baseline(using paired t-test) for Cell 1 (Hydration+REDEFINE, formulation1505-21). However, a statistically significant decrease (indicating animprovement in skin roughness) was observed in maximum roughness atweeks 4 and 8, in average roughness at week 8, in smoothness depth atweek 4, and in arithmetic average roughness at week 4 for Cell 2(Hydration+REVERSE, formulation 1505-42B) from baseline. See FIG. 19,top VisioScan image is baseline and the bottom VisioScan image is 8weeks after treatment with formulation 1505-42B.

What is claimed:
 1. An interpenetrating polymer network moisturizingtopical composition comprising: about 0.01% w/w to about 5% w/w ofcrosslinked gellan gum; about 0.01% w/w to about 5% w/w of cetylhydroxyethylcellulose; about 0.01% w/w to about 5% w/w of sodiumhyaluronate; about 0.01% w/w to about 5% w/w of a mono-, or di-valention; and about 25% w/w to about 80% w/w of a humectant selected fromglycerin, diglycerin, and a combination thereof; wherein the cetylhydroxyethylcellulose and the sodium hyaluronate are interlaced; andwherein the crosslinked gellan gum is crosslinked via ionic bonds,through the mono-, or di-valent ion, and entraps the interlaced cetylhydroxyethylcellulose, the sodium hyaluronate, and the humectant to formthe interpenetrating polymer network moisturizing topical composition.2. The moisturizing topical composition of claim 1, wherein the mono-,or di-valent ion is selected from the group consisting of2-Pyrrolidone-5-Carboxylic Acid (PCA), calcium PCA, sodium PCA, zincPCA, magnesium PCA, sea salt, inorganic salts of citric acid, inorganicsalts of lactic acid, calcium ascorbate, magnesium ascorbate, calciumoxide, calcium benzoate, calcium sorbate, calcium aspartate, magnesiumcarbonate, magnesium chloride, magnesium nitrate, and any combinationthereof.
 3. The moisturizing topical composition of claim 1, wherein themoisturizing composition is selected from the group consisting ofliquid, solution, emulsion, suspension, triturate, jelly, foam, paste,ointment, shampoo, adhesive, cream, serum, milk, lotion, salve, oil,butter, gel, and balm.
 4. A method of treating dry and/or irritated skincomprising administering an interpenetrating polymer networkmoisturizing topical composition comprising: about 0.01% w/w to about 5%w/w of crosslinked gellan gum; about 0.01% w/w to about 5% w/w of cetylhydroxyethylcellulose; about 0.01% w/w to about 5% w/w of sodiumhyaluronate; about 0.01% w/w to about 5% w/w of a mono-, or di-valention; and about 25% w/w to about 80% w/w of a humectant selected fromglycerin, diglycerin, and a combination thereof; wherein the cetylhydroxyethylcellulose and the sodium hyaluronate are interlaced; andwherein the crosslinked gellan gum is crosslinked via ionic bonds,through the mono-, or di-valent ion, and entraps the interlaced cetylhydroxyethylcellulose, the sodium hyaluronate, and the humectant to formthe interpenetrating polymer network moisturizing topical composition.5. The method of claim 4, wherein the mono-, or di-valent ion isselected from the group consisting of 2-Pyrrolidone-5-Carboxylic Acid(PCA), calcium PCA, sodium PCA, zinc PCA, magnesium PCA, sea salt,inorganic salts of citric acid, inorganic salts of lactic acid, calciumascorbate, magnesium ascorbate, calcium oxide, calcium benzoate, calciumsorbate, calcium aspartate, magnesium carbonate, magnesium chloride,magnesium nitrate, and any combination thereof.
 6. The method of claim4, wherein the moisturizing composition is a formulation selected fromthe group consisting of liquid, solution, emulsion, suspension,triturate, jelly, foam, paste, ointment shampoo, adhesive, cream, serum,milk, lotion, salve, oil, butter, gel, and balm.
 7. A method ofproducing a interpenetrating polymer network moisturizing topicalcomposition, the method comprising: dispersing a non-crosslinked gellangum capable of crosslinking in water to form a first phase; combiningsodium hyaluronate and cetyl hydroxyethylcellulose with a humectantselected from glycerin, diglycerin, and a combination thereof to form asecond phase; combining the first and second phases to form a thirdphase of uncrosslinked interlaced gellan gum, sodium hyaluronate, andcetyl hydroxyethylcellulose; adding a mono-valent, di-valent ion or acombination thereof to the third phase to crosslink the gellan gum toform the interpenetrating polymer network moisturizing topicalcomposition, wherein the interpenetrating polymer network moisturizingtopical composition is made up of a crosslinked gellan gum in a threedimensional structure, sodium hyaluronate, cetyl hydroxyethylcellulose,and the humectant; wherein the crosslinked gellan gum entraps theinterlaced sodium hyaluronate, cetyl hydroxyethylcellulose, and thehumectant, and wherein the crosslinked gellan gum is crosslinked viaionic bonds wherein the composition comprises about 0.01% w/w to about5% w/w of crosslinked gellan gum; about 0.01% w/w to about 5% w/w ofcetyl hydroxyethylcellulose; about 0.01% w/w to about 5% w/w of sodiumhyaluronate; about 0.01% w/w to about 5% w/w of the mono-, or di-valention; and about 25% w/w to about 80% w/w of the humectant.
 8. The methodof claim 7, the mono-valent, di-valent ion is selected from groupconsisting of 2-Pyrrolidone-5-Carboxylic Acid (PCA), calcium PCA, sodiumPCA, zinc PCA, magnesium PCA, sea salt, inorganic salts of citric acid,inorganic salts of lactic acid, calcium ascorbate, magnesium ascorbate,calcium oxide, calcium benzoate, calcium sorbate, calcium aspartate,magnesium carbonate, magnesium chloride, magnesium nitrate, and anycombination thereof.
 9. A drug or active ingredient delivery systemcomprising: about 0.01% w/w to about 5% w/w of crosslinked gellan gum;about 0.01% w/w to about 5% w/w of cetyl hydroxyethylcellulose; about0.01% w/w to about 5% w/w of sodium hyaluronate; about 0.01% w/w toabout 5% w/w of a mono-, or di-valent ion; about 25% w/w to about 80%w/w of a humectant selected from glycerin, diglycerin, and a combinationthereof; and a drug or active ingredient; wherein the cetylhydroxyethylcellulose and the sodium hyaluronate are interlaced; andwherein the crosslinked gellan gum is crosslinked via ionic bonds,through the mono-, or di-valent ion, and entraps the cetylhydroxyethylcellulose, the sodium hyaluronate, the humectant, and thedrug or active ingredient to form the interpenetrating polymer networkmoisturizing topical composition.
 10. The drug or active ingredientdelivery system of claim 9, wherein the mono-, or di-valent ion isselected from the group consisting of 2-Pyrrolidone-5-Carboxylic Acid(PCA), calcium PCA, sodium PCA, zinc PCA, magnesium PCA, sea salt,inorganic salts of citric acid, inorganic salts of lactic acid, calciumascorbate, magnesium ascorbate, calcium oxide, calcium benzoate, calciumsorbate, calcium aspartate, magnesium carbonate, magnesium chloride,magnesium nitrate, and any combination thereof.
 11. The drug or activeingredient delivery system of claim 9, wherein the drug or activeingredient is selected from the group consisting of benzoyl peroxide,salicylic acid, willowbark extract, poly hydroxyacid, tannic acid,hydroxybenzoic acid, juniperic acid, tartaric acid, glycolic acid,lactic acid, citric acid, retinol, antioxidants, vitamin A, retinoid,tretinoin, tazarotene, ibuprofen, diclofenac, felbinac, ketoprofen,piroxicam and any combination thereof.
 12. The moisturizing topicalcomposition of claim 1, wherein the mono-, or di-valent ion is selectedfrom calcium PCA, magnesium PCA, and combinations thereof.
 13. Themoisturizing topical composition of claim 1, wherein the humectant is inan amount of about 30%.
 14. The moisturizing topical composition ofclaim 1, wherein the humectant is glycerin and is in an amount of about30%.
 15. The moisturizing topical composition of claim 1, wherein theviscosity of the moisturizing topical composition is about 400 to about1400 cps.
 16. The moisturizing topical composition of claim 1, whereinthe gellan gum is in an amount of about 0.11% w/w, the cetylhydroxyethylcellulose is in an amount of about 0.30% w/w, the sodiumhyaluronate is in an amount of about 0.12% w/w, the mono-, or di-valention is a combination of magensium PCA in an amount of about 0.30% w/wand calcium PCA in an amount of about 0.30% w/w, and the humectant isglycerin in an amount of about 30% w/w.